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1.
Comparison of continuous local anaesthetic and systemic pain treatment after axillary lymphadenectomy in breast carcinoma patients - a prospective randomized study
Branka Stražišar, Nikola Bešić, 2013, izvirni znanstveni članek

Povzetek: Background. Acute pain after axillary lymphadenectomy is often related mainly to axillary surgery. The aim of the prospective randomized study was to find out if continuous wound infusion of local anaesthetic reduces postoperative pain, consumption of opioids and the incidence of chronic pain compared to the standard intravenous piritramide analgesia after axillary lymphadenectomy in breast carcinoma patients. Methods. Altogether 60 patients were enrolled in the prospective randomized study; half in wound infusion of local anaesthetic and half in the standard (piritramide) group. Results. In the recovery room and on the first day after surgical procedure, the wound infusion of local anaesthetic group reported less acute and chronic pain, a lower consumption of piritramide and metoclopramide, but their alertness after the surgical procedure was higher compared to the standard group. Conclusions. After axillary lymphadenectomy in breast carcinoma patients, wound infusion of local anaesthetic reduces acute pain and enables reduced opioid consumption, resulting in less postoperative sedation and a reduced need for antiemetic drugs. After wound infusion of local anaesthetic there is a statistical trend for reduction of chronic pain.
Ključne besede: breast carcinoma, pain treatment, acute pain
Objavljeno v DiRROS: 22.03.2024; Ogledov: 39; Prenosov: 19
.pdf Celotno besedilo (442,59 KB)

2.
Gene immunotherapy of colon carcinoma with IL-2 and IL-12 using gene electrotransfer
Tilen Komel, Maša Omerzel, Urška Kamenšek, Katarina Žnidar, Urša Lampreht Tratar, Simona Kranjc Brezar, Klemen Dolinar, Sergej Pirkmajer, Gregor Serša, Maja Čemažar, 2023, izvirni znanstveni članek

Povzetek: Gene immunotherapy has become an important approach in the treatment of cancer. One example is the introduction of genes encoding immunostimulatory cytokines, such as interleukin 2 and interleukin 12, which stimulate immune cells in tumours. The aim of our study was to determine the effects of gene electrotransfer of plasmids encoding interleukin 2 and interleukin 12 individually and in combination in the CT26 murine colon carcinoma cell line in mice. In the in vitro experiment, the pulse protocol that resulted in the highest expression of IL-2 and IL-12 mRNA and proteins was used for the in vivo part. In vivo, tumour growth delay and also complete response were observed in the group treated with the plasmid combination. Compared to the control group, the highest levels of various immunostimulatory cytokines and increased immune infiltration were observed in the combination group. Long-term anti-tumour immunity was observed in the combination group after tumour re-challenge. In conclusion, our combination therapy efficiently eradicated CT26 colon carcinoma in mice and also generated strong anti-tumour immune memory.
Ključne besede: colon carcinoma, gene electrotransfer, gene immunotherapy
Objavljeno v DiRROS: 21.03.2024; Ogledov: 71; Prenosov: 43
.pdf Celotno besedilo (6,92 MB)
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3.
CT colonography in detection of colorectal carcinoma
Amela Sofić, Šerif Beslić, Igor Kocijančič, Nedžad Šehović, 2010, izvirni znanstveni članek

Povzetek: Background. Diagnostic methods used in screening and detectingand 2 lipomas,and 2 lipomas, among tumours there were 55 adenocarcinomas and 1 lymphoma. Results showed CT colonography among tumours there were 55 adenocarcinomas and 1 lymphoma. Results showed CTsensitivity to polyps to be 89.7%, barium enema 48.7%, and colonoscopy 94.9%. Sensitivity to tumours of CT colonography colonography colorectal CT barium enema followed by colonoscopy wereand colonoscopy was 100% and of barium enema 94.6%. Specificities and PPV were 100% in all procedures. The performed. After thesensitivity to polyps to be 89.7%, barium enema 48.7%, andcomfort assessment showed CT colonography as the far most comfortable out of three procedures. colonoscopy 94.9%. Sensitivity to tumours of CT colonography procedures a comfort assessment was done in all colonography. The aim of thisand colonoscopy was 100% and of barium enema 94.6%. Specificities and PPV were 100% in all procedures. The study was to establish diagnostic accuracy andpatients. Diagnostic positive comfort assessment showed CT colonography as the far most comfortable out of three procedures. results were verified by the pato-histological examination. Sensitivity, specificity, positive comfort of CT colonography compared carcinoma are digitorectal examination,topredicative value (PPV) and negative predicative value (NPV) were calculated for each procedure.
Ključne besede: CT colonography, barium enema, colonoscopy, colorectal polyp, colorectal carcinoma
Objavljeno v DiRROS: 18.03.2024; Ogledov: 53; Prenosov: 20
.pdf Celotno besedilo (933,29 KB)

4.
Medullary thyroid carcinoma and associated endocrinopathies in Slovenia from 1995 to 2021
Sara Milićević, Mateja Krajc, Ana Blatnik, Barbara Perić, 2022, izvirni znanstveni članek

Povzetek: Background: Medullary thyroid cancer (MTC) is a rare endocrine tumour that is sporadic in 75% of cases and occurs as a part of inherited cancer syndromes in approximately 25% of cases. The aim of this study was to determine the frequency and type of RET pathogenic variants (PVs) in the Slovenian MTC patient population diagnosed between 1995 and 2021 and to elucidate the full range of associated endocrinopathies. Methods: A retrospective analysis of medical records of 266 MTC patients and their relatives seen in a tertiary centre between 1995 and 2021 was performed. Sequence analysis of exons 10, 11, 13, 14, 15, and 16 of the RET gene was analysed in most patients using Sanger sequencing. From 2017, the entire sequence of RET gene was analysed in most patients using targeted next-generation sequencing. Results: Germline PVs in the RET proto-oncogene were identified in 21.6% probands from 21 different MTC families. Of their tested relatives, 65% (67/103) were RET-positive and 35% (36/103) were RET-negative. PVs were detected in codon 618 and codon 634 in 28.6%, and in codon 790 in 23.8%. The RET-positive group consisted of 52 MTC patients, 13 patients with C cell hyperplasia and 2 individuals with neither. Associated endocrinopathies were diagnosed in 8/21 families: primary hyperparathyroidism (PHPT) in six families and pheochromocytoma (PHEO) in five families. In 62% of RET-positive families (13/21), no associated endocrinopathies were diagnosed. PHEO was most commonly associated with C634R (6/13) and PHPT with C634R (4/7). Hirschsprung’s disease appeared in one patient with RET PV in codon 618. Based on data from the Cancer Registry of Republic of Slovenia, only individual cases of common cancers with well understood environmental risk factors were discovered; lung cancer in 2/21 of families, papillary thyroid cancer in 3/21 of families, cutaneous melanoma in 2/21 of families, cervical cancer in 1/21 families, and lymphoma in 1/21 families. Conclusions: Analysis of prospectively collected MTC cases during a 27-year period revealed that 21.6% of Slovenian patients are RET PV carriers. Sixty-two percent of families had none of the associated endocrinopathies, confirming the thesis that FMTC is the most common presentation. This could suggest using risk-stratified management approaches when screening for PHEO and PHPT in RET PV carriers. However, more studies are needed to evaluate potential genetic risk modifiers as well as safety, improved quality of life, and medical cost reduction in the case of a patient-oriented approach.
Ključne besede: medullary thyroid carcinoma, multiple endocrine neoplasia, primary hyperparathyroidism
Objavljeno v DiRROS: 23.09.2022; Ogledov: 504; Prenosov: 237
.pdf Celotno besedilo (248,03 KB)
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5.
Real-world testing practices, treatment patterns and clinical outcomes in patients from Central Eastern Europe with EGFR-mutated advanced non-small cell lung cancer : a retrospective chart review study (REFLECT)
Urška Janžič, Nina Turnšek, Mircea Dediu, Ivan Shterev Donev, Roxana Lupu, Gabriela Teodorescu, Tudor Ciuleanu, Adam Płużański, 2022, izvirni znanstveni članek

Povzetek: The targeted therapy with tyrosine kinase inhibitors (TKIs) against the epidermal growth factor receptor mutation (EGFRm) in advanced non-small cell lung cancer (NSCLC) changed the treatment paradigm. REFLECT study (NCT04031898) explored EGFR/T790M testing and treatment patterns in EGFRm NSCLC patients receiving first- or second-generation (1G/2G) EGFR TKIs as front-line (1L) in eight countries. Pooled data from Central Eastern Europe (CEE) countries from this study (Bulgaria, Poland, Romania, Slovenia) are presented here. This physician-led chart review study was conducted in patients with confirmed-EGFRm NSCLC initiating 1L 1G/2G EGFR TKIs between 2015–2018. The CEE cohort included 389 patients receiving 1L erlotinib (37%), afatinib (34%), and gefitinib (29%). Overall, 320 (82%) patients discontinued 1L, and 298 (77%) progression events were registered. Median progression free survival on 1L TKIs was 14.0 (95% CI: 12.6–15.6) months. Median overall survival from 1L start was 26.6 (95% CI: 24.1–29.0) months. Attrition rate between 1L and next line was 30%. Among patients with 1L progression, 200 (67%) were tested for T790M and 58% were positive. This first CEE analysis of treatments and outcomes in EGFRm NSCLC patients highlights the importance of using the most efficacious therapies currently available in 1L to reduce attrition and improve patient outcomes.
Ključne besede: lung neoplasms, non-small cell lung carcinoma, Eastern Europe, real-world study, REFLECT study, epidermal growth factor receptor, lung cancer
Objavljeno v DiRROS: 09.09.2022; Ogledov: 475; Prenosov: 193
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6.
Neuroendocrine carcinoma of the larynx and pharynx : a clinical and histopathological study
Primož Strojan, Robert Šifrer, Alfio Ferlito, Cvetka Grašič-Kuhar, Boštjan Lanišnik, Gaber Plavc, Nina Zidar, 2021, izvirni znanstveni članek

Povzetek: Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995%2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein%Barr virus (EBV) was performed. Twenty patients (larynx, 12; pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs % 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is needed; the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.
Ključne besede: electrochemotherapy, head and neck cancer, neuroendocrinic carcinoma
Objavljeno v DiRROS: 07.09.2022; Ogledov: 468; Prenosov: 211
.pdf Celotno besedilo (3,97 MB)
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7.
Vismodegib in locally advanced basal cell carcinoma in Slovenia
Tanja Mesti, Maša Sever, Janja Ocvirk, 2022, izvirni znanstveni članek

Povzetek: Background: Vismodegib is a first-in-class inhibitor of the hedgehog pathway for treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC. Objectives: The purpose of this study is to report outcomes of patients with laBCC, with basal cell carcinoma nevus syndrome (Gorlin Goltz syndrome [G-G Syn]) treated with vismodegib in routine clinical practice in Slovenia in 8.3-year period. Methods: In this retrospective cohort study, we analyzed baseline characteristics, outcomes, and treatment-related adverse events from locally advanced BCC. The patients were divided into two cohorts: 39 laBCC or multiple BCC patients and 7 patients with G-G Syn who were treated with vismodegib from November 2012 till January 2021. Results: During 100-month period, 46 patients were diagnosed with laBCC (26), multiple BCC (13), and G-G Syn (7), all inappropriate for surgery or radiotherapy. Baseline characteristics: median age was 72.8 years in laBCC + multiple BCC cohort and 47.4 years in G-G Syn cohort. The objective response rate was 80% in laBCC + multiple BCC and 86% in G-G Syn cohort. Disease control rate (DCR) was 95% in laBCC + multiple BCC and 100% in G-G Syn cohort. Median duration of treatment was 9.9 months (range: 1.5-43.1) in laBCC and multiple BCC cohort and 19.5 months (range: 3.6-94.1) in G-G Syn cohort. Majority of treatment-emergent adverse events (TEAEs) in laBCC or multiple BCC cohort were grade 1 or 2 (96%), only 4% of AEs were grade 3. Majority of TEAEs in G-G Syn cohort were also grade 1 or 2 (87%), 13% of AEs were grade 3. No grade 4 or 5 vismodegib-related AEs were reported. Conclusion: Vismodegib has shown meaningful efficacy with DCR from 95% to 100% in patients with laBCC, multiple BCC, and G-G Syn in Slovenia. TEAEs were successfully alleviated with multidisciplinary approach and early supportive care.
Ključne besede: basal cell carcinoma, early supportive care, Gorlin Goltz syndrome, multidisciplinary approach
Objavljeno v DiRROS: 07.09.2022; Ogledov: 429; Prenosov: 203
.pdf Celotno besedilo (448,27 KB)
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8.
Real-world experience with capmatinib in MET exon 14-mutated non-small cell lung cancer (RECAP) : a retrospective analysis from an early access program
Oliver Illini, Hannah Fabikan, Aurélie Swalduz, Anders Vikström, Dagmar Krenbek, Michael Schumacher, Elizabeth Dudnik, Michael Studnicka, Ronny Öhman, Robert Wurm, Tanja Čufer, Katja Mohorčič, Maximilian J Hochmair, 2022, izvirni znanstveni članek

Povzetek: Background: Patients with non-small cell lung cancer (NSCLC) presenting with mesenchymal–epithelial transition (MET) exon 14 skipping mutation have an unfavorable prognosis with standard treatments. Capmatinib is a selective MET inhibitor, which showed promising efficacy in this patient population in early trials. Methods: We performed a retrospective, international, multicenter efficacy and safety analysis in patients with NSCLC treated with capmatinib in an early access program between March 2019 and December 2021. Results: Data from 81 patients with advanced MET exon 14 mutated NSCLC treated with capmatinib in first- or later-line therapy were analyzed. Median age was 77years (range, 48–91), 56% were women, 86% had stage IV disease, and 27% had brain metastases. For all patients, the objective response rate (ORR) to capmatinib was 58% (95% CI, 47–69), whereas it was 68% (95% CI, 50–82) in treatment-naïve and 50% (95% CI, 35–65) in pretreated patients. The median progression-free survival was 9.5months (95% CI, 4.7–14.3), whereas it was 10.6months (95% CI, 5.5–15.7) in first-line and 9.1months (95% CI, 3.1–15.1) in pretreated patients. After a median follow-up of 11.0months, the median overall survival was 18.2 months (95% CI, 13.2–23.1). In patients with measurable brain metastases (n=11), the intracranial ORR was 46% (95% CI, 17–77). Capmatinib showed a manageable safety profile. Grade⩾3 treatment-related adverse events included peripheral edema (13%), elevated creatinine (4%), and elevated liver enzymes (3%). Conclusion: In patients with MET exon 14 skipping mutation, capmatinib showed durable systemic and intracranial efficacy and a manageable safety profile. This analysis confirms previously reported phase II data in a real-world setting.
Ključne besede: non-small cell lung carcinoma -- drug therapy -- genetics, molecular targeted therapy, real-world data, capmatinib, targeted therapy
Objavljeno v DiRROS: 24.06.2022; Ogledov: 703; Prenosov: 541
.pdf Celotno besedilo (943,38 KB)
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9.
Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small cell lung cancer : an international multicenter study
Zsolt Megyesfalvi, Nandor Barany, Andras Lantos, Zsuzsanna Valko, Orsolya Pipek, Christian Lang, Anna Schwendenwein, Felicitas Oberndorfer, Sandor Paku, Bence Ferencz, Izidor Kern, Mile Kovačević, Viktoria Laszlo, Balazs Dome, 2022, izvirni znanstveni članek

Povzetek: The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant) and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we have investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1 and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines reveal distinct vulnerability profiles defined by transcription regulators.
Ključne besede: Non-small-cell lung carcinoma, immunohistochemistry, molecular subtypes, prognostic relevance, expression pattern, neuroendocrine subtypes
Objavljeno v DiRROS: 27.05.2022; Ogledov: 808; Prenosov: 1210
.pdf Celotno besedilo (4,37 MB)
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10.
Treatment patterns, testing practices, and outcomes in the pre-FLAURA era for patients with EGFR mutation-positive advanced NSCLC : a retrospective chart review (REFLECT)
Alfredo Addeo, Maximilian J Hochmair, Urška Janžič, Elizabeth Dudnik, Andriani Charpidou, Adam Płużański, Tudor Ciuleanu, Ivan Shterev Donev, Judith Elbaz, Jørgen Aarøe, René Ott, Nir Peled, 2021, izvirni znanstveni članek

Povzetek: Background. Immunotherapy with immune checkpoint inhibitors (ICIs) recently became the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). Here, we present the first results of a real-world observational study on the effectiveness of ICI monotherapy in patients with advanced NSCLC treated at a single academic center in a Central and Eastern European (CEE) country. Materials and methods. Overall, 66 consecutive patients with advanced NSCLC treated with ICIs in everyday clinical practice, either with first-line pembrolizumab (26 patients) or second-line atezolizumab, nivolumab, or pembrolizumab (40 patients), from August 2015 to November 2018, were included. All data were retrieved from a hospital lung cancer registry, in which the data is collected prospectively. Results. Included patients had a median age of 64 years, most were male (55%), 6% were in performance status >/=2, and 18% had controlled central nervous system metastases at baseline. In first-line, the median progression-free survival (mPFS) was 9.3 months, while the median overall survival (mOS) was not reached. The 1-year overall survival (OS) was 62%. In second-line, the mPFS and mOS were 3.5 months and 9.9 months, respectively, with a 1-year OS of 35%. In the overall population, adverse events of any grade were recorded in 79% of patients and of severe grade (3-4) in 12% of patients. Conclusion. The first real-world outcomes of NSCLC immunotherapy from a CEE country suggest comparable effectiveness to those observed in clinical trials and other real-world series, mainly coming from North America and Western European countries. Further data to inform on the real-world effectiveness of immunotherapy worldwide are needed.
Ključne besede: non-small cell lung carcinoma, immunotherapy, advanced non-small cell lung cancer, real-world data, Europe, Central Europe, Eastern Europe
Objavljeno v DiRROS: 15.12.2021; Ogledov: 769; Prenosov: 405
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