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92. Lack of association between cortical amyloid deposition and glucose metabolism in early stage Alzheimer's disease patientsDaniela Ehrlich, Andreas Dunzinger, Gertraud Malsiner-Walli, Bettina Grün, Raffi Topakian, Marina Hodolič, Elmar Kainz, Robert Pichler, 2022, original scientific article Published in DiRROS: 24.07.2024; Views: 188; Downloads: 99
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93. Pre-treatment risk assessment of women with endometrial cancer: differences in outcomes of molecular and clinical classifications in the Slovenian patient cohortJure Knez, Monika Sobočan, Urška Belak Magdalenić, Rajko Kavalar, Mateja Zupin, Tomaž Büdefeld, Uroš Potočnik, Iztok Takač, 2022, original scientific article Published in DiRROS: 24.07.2024; Views: 211; Downloads: 184
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95. Disease control with prior platinum-based chemotherapy is prognostic for survival in patients with metastatic urothelial cancer treated with atezolizumab in real-world practiceMarina Mencinger, Dushan Mangaroski, Urška Bokal, 2021, original scientific article Abstract: Background. Atezolizumab, a programmed-death ligand-1 (PD-L1) inhibitor, is a novel treatment option for patients with metastatic urothelial cancer (mUC). Clinical prognostic factors, survival outcomes, and the safety of patients with mUC treated with atezolizumab, in a real-world setting, were investigated.Patients and methods. 62 patients with mUC, treated at the Institute of Oncology Ljubljana between May 8th 2018 and Dec 31st 2019, were included. Response rates and immune-related adverse events (irAE) were collected. Progression-free survival and overall survival times were assessed using the Kaplan-Meier method. The Cox propor-tional hazards model was applied to identify the factors affecting survival. Results. Of 62 patients, five (8.1%) have not yet been evaluated and 20 (32%) died prior to the first radiographic evaluation. We observed clinical benefit in 19 (33%), objective response in 12 (21%), and complete response in five (9%) patients. Median overall survival for the whole population was 6.8 (95% CI, 2.6–11.0), for platinum-naïve 8.7 (95% CI: 0.8–16.5), and for the platinum-treated group 6.8 (95% CI, 3.7–10) months. At the 5.8 (0.3–23.1) month median follow-up, the median duration of the response was not reached. IrAE occurred in 20 (32%) patients and seven (11%) of them discontinued the treatment. Multivariate analysis in platinum-treated patients showed that a treatment-free interval of more than six months was prognostic for overall survival (OS). Conclusions. Responses to atezolizumab led to long disease remission in a subset of our patients. The median OS in our real-world population was compromised by a large percentage of patients with poor ECOG performance status (PS). A treatment-free interval from chemotherapy was associated with the longer survival of platinum-treated pa-tients with mUC receiving further atezolizumab.
Keywords: PD-L1 inhibitor, urothelial cancer, bladder, atezolizumab
Published in DiRROS: 23.07.2024; Views: 207; Downloads: 116
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96. Clinical outcomes in stage III non-small cell lung cancer patients treated with durvalumab after sequential or concurrent platinum-based chemoradiotherapy : single institute experienceMartina Vrankar, Karmen Stanič, Staša Jelerčič, Eva Ćirić, Ana Lina Vodušek, Jasna But-Hadžić, 2021, original scientific article Abstract: Chemoradiotherapy (ChT-RT) followed by 12-month durvalumab is the new standard treatment for unresectable stage III non-small cell lung cancer. Survival data for patients from everyday routine clinical practice is scarce, as well as potential impact on treatment efficacy of sequential or concomitant chemotherapy and the us-age of gemcitabine.Patients and methods. We retrospectively analysed unresectable stage III NSCLC patients who were treated with durvalumab after radical concurrent or sequential chemotherapy (ChT) from December 2017 and completed treat-ment until December 2020. We assessed progression free survival (PFS), overall survival (OS) and toxicity regarding baseline characteristic of patients.Results. Eighty-five patients with median age of 63 years of which 70.6% were male, 56.5% in stage IIIB and 58.8% with squamous cell carcinoma, were included in the analysis. Thirty-one patients received sequential ChT only, 51 patients received induction and concurrent ChT and 3 patients received concurrent ChT only. Seventy-nine patients (92.9%) received gemcitabine and cisplatin as induction chemotherapy and switched to etoposide and cisplatin during con-current treatment with radiotherapy (RT). Patients started durvalumab after a median of 57 days (range 12–99 days) from the end of the RT and were treated with the median of 10.8 (range 0.5–12 months) months. Forty-one patients (48.2%) completed treatment with planned 12-month therapy, 25 patients (29.4%) completed treatment early due to the toxicity and 16 patients (18.8%) due to the disease progression. Median PFS was 22.0 months, 12- and estimated 24-month PFS were 71% (95% CI: 61.2–80.8%) and 45.8% (95% CI: 32.7–58.9%). With the median follow-up time of 23 months (range 2–35 months), median OS has not been reached. Twelve- and estimated 24-month OS were 86.7% (95% CI: 79.5–93.9%) and 68.6% (95% CI: 57.2–79.9%).Conclusions. Our survival data are comparable with published research as well as with recently published real-world reports. Additionally, the regimen with gemcitabine and platinum-based chemotherapy as induction treatment was efficient and well tolerated.
Keywords: non-small cell lung cancer, stage III, chemoradiotherapy, durvalumab, acute toxicity
Published in DiRROS: 23.07.2024; Views: 229; Downloads: 50
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97. Preoperative intensity-modulated chemoradiotherapy with simultaneous integrated boost in rectal cancer : five-year follow-up results of a phase II studyJasna But-Hadžić, Anja Meden Boltežar, Tina Škerl, Vesna Zadnik, Vaneja Velenik, 2021, original scientific article Abstract: We conducted a phase II study to investigate the feasibility and safety of preoperative radiochemo-therapy experimental fractionation, using intensity-modulated radiation therapy with simultaneous integrated boost (IMRT SIB) to shorten the overall treatment time without dose escalation in intermediate/locally advanced rectal cancer with the aim to improving treatment outcome.Patients and methods. A total of 51 patients with operable stage II–III rectal carcinoma were included between January 2014 and January 2015. Fifty patients completed preoperative IMRT treatment with an elective dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/T3 and 48.4 Gy to T4 tumour in 22 fractions, with concomitant capecit-abine (825 mg/m2/12 h, including at weekends). Median follow-up was 70 months (range 11–80 m).Results. Forty-seven patients completed treatment per protocol. Acute toxicity occurred in 2 (4%) patients. R0 resec-tion was achieved in all but 1 and pathologic complete response (pCR) in 12 (25.5%) patients who had 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) of 91.7%, 100% and 100%, respectively. The intention-to-treat analysis showed that the type of surgery significantly moderated OS and DFS, while total downstaging and pN were predictive for DFS only. For treatment per protocol 5-year OS, DFS and LC were 80.9% (95% confidence interval [CI] 69.7–92.1), 77.1% (95% CI 65.1–89.1) and 95.2% (95% CI 88.7–100), respectively. The proportion of patients with severe late (CTCAE G ≥ 3) gastrointestinal, urinary and sexual toxicity was 15%, 2% and 8% respectively, with one reported secondary carcinoma.
Keywords: rectal cancer, IMRT, simultaneous integrated boost, preoperative radiochemotherapy, acute toxicity
Published in DiRROS: 23.07.2024; Views: 197; Downloads: 74
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98. Diagnostic performance of p16/Ki-67 dual immunostaining at different number of positive cells in cervical smears in women referred for colposcopyUršula Salobir Gajšek, Andraž Dovnik, Iztok Takač, Urška Ivanuš, Tine Jerman, Simona Šramek Zatler, Alenka Repše-Fokter, 2021, original scientific article Abstract: . The aim of the study was to evaluate the diagnostic accuracy of p16/Ki-67 dual immunostaining (p16/ Ki-67 DS) in cervical cytology and the number of positive p16/Ki-67 cells to diagnose high grade cervical intraepithelial neoplasia (CIN2+) in colposcopy population. Subjects and methods. We performed an analysis on a subset cohort of 174 women enrolled within a large-scale randomised controlled human papillomavirus (HPV) self-sampling project organised as part of the population-based Cervical Cancer Screening Programme ZORA in Slovenia. This subset cohort of patients was invited to the colposcopy clinic, underwent p16/Ki-67 DS cervical cytology and had the number of p16/Ki-67 positive cells determined. Results. Among analysed women, 42/174 (24.1%) had histologically confirmed CIN2+. The risk for CIN2+ was increasing with the number of positive cells (p < 0.001). The sensitivity of p16/Ki-67 DS for detection of CIN2+ was 88.1%, specificity was 65.2%, positive predictive value was 44.6% and negative predictive value was 94.5%. Conclusions. Dual p16/Ki-67 immunostaining for the detection of CIN2+ has shown high sensitivity and high negative predictive value in our study, which is comparable to available published data. The number of p16/Ki-67 positive cells was significantly associated with the probability of CIN2+ detection. We observed a statistically significant and clinically relevant increase in specificity if the cut-off for a positive test was shifted from one cell to three cells.
Keywords: cervical cytology, high-grade dysplasia, p16/Ki-67 immunostaining
Published in DiRROS: 22.07.2024; Views: 211; Downloads: 76
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99. MitomiRs: their roles in mitochondria and importance in cancer cell metabolismAndrej Renčelj, Nada Gvozdenović, Maja Čemažar, 2021, review article Abstract: Background. MicroRNAs (miRNAs) are short non-coding RNAs that play important roles in almost all biological path- ways. They regulate post-transcriptional gene expression by binding to the 3%untranslated region (3%UTR) of messenger RNAs (mRNAs). MitomiRs are miRNAs of nuclear or mitochondrial origin that are localized in mitochondria and have a crucial role in regulation of mitochondrial function and metabolism. In eukaryotes, mitochondria are the major sites of oxidative metabolism of sugars, lipids, amino acids, and other bio-macromolecules. They are also the main sites of adenosine triphosphate (ATP) production. Conclusions. In the review, we discuss the role of mitomiRs in mitochondria and introduce currently well studied mito- miRs, their target genes and functions. We also discuss their role in cancer initiation and progression through the regu- lation of mRNA expression in mitochondria. MitomiRs directly target key molecules such as transporters or enzymes in cell metabolism and regulate several oncogenic signaling pathways. They also play an important role in the Warburg effect, which is vital for cancer cells to maintain their proliferative potential. In addition, we discuss how they indirectly upregulate hexokinase 2 (HK2), an enzyme involved in glucose phosphorylation, and thus may affect energy metabo- lism in breast cancer cells. In tumor tissues such as breast cancer and head and neck tumors, the expression of one of the mitomiRs (miR-210) correlates with hypoxia gene signatures, suggesting a direct link between mitomiR expression and hypoxia in cancer. The miR-17/92 cluster has been shown to act as a key factor in metabolic reprogramming of tumors by regulating glycolytic and mitochondrial metabolism. This cluster is deregulated in B-cell lymphomas, B-cell chronic lymphocytic leukemia, acute myeloid leukemia, and T-cell lymphomas, and is particularly overexpressed in several other cancers. Based on the current knowledge, we can conclude that there is a large number of miRNAs present in mitochondria, termed mitomiR, and that they are important regulators of mitochondrial function. Therefore, mitomiRs are important players in the metabolism of cancer cells, which need to be further investigated in order to develop a potential new therapies for cancer.
Keywords: microRNAs, mitomiR, mitochondria, cancer cell metabolism
Published in DiRROS: 22.07.2024; Views: 238; Downloads: 88
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