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1.
PD-L1 expression in squamous-cell carcinoma and adenocarcinoma of the lung
Urška Janžič, Izidor Kern, Andrej Janžič, Luka Čavka, Tanja Čufer, 2017, original scientific article

Abstract: With introduction of immunotherapy (IT) into the treatment of advanced non-small-cell lung cancer (NSCLC), a need for predictive biomarker became apparent. Programmed death ligand 1 (PD-L1) protein expression is most widely explored predictive marker for response to IT. We assessed PD-L1 expression in tumor cells (TC) and immune cells (IC) of squamous-cell carcinoma (SCC) and adenocarcinoma (AC) patients. We obtained 54 surgically resected tumor specimens and assessed PD-L1 expression by immunohistochemistry after staining them with antibody SP142 (Ventana, USA). Clinicopathological characteristics were acquired from the hospital registry database. Results were analyzed according to cut-off values of % 5% and % 10% of PD-L1 expression on either TC or IC. 29 (54%) samples were AC and 25 (46%) were SCC. PD-L1 expression was significantly higher in TC of SCC compared to AC at both cut-off values (52% vs. 17%, p = 0.016 and 52% vs. 14%, p = 0.007, respectively) no difference in PD-L1 expression in IC of SCC and AC was found. In AC alone, PD-L1 expression was significantly higher in IC compared to TC at both cut-off values (72% vs. 17%, p < 0.001 and 41% vs. 14%, p = 0.008, respectively), while no significant difference between IC and TC PD-L1 expression was revealed in SCC. Our results suggest a significantly higher PD-L1 expression in TC of SCC compared to AC, regardless of the cut-off value. PD-L1 expression in IC is high in both histological subtypes of NSCLC, and adds significantly to the overall positivity of AC but not SCC.
Keywords: lung cancer, squamous-cell lung cancer, adenocarcinoma, tumor cells, immune cells, PD-L1 expression
Published in DiRROS: 31.05.2024; Views: 41; Downloads: 36
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Long term results of radiotherapy in vulvar cancer patients in Slovenia between 1997-2004
Helena Barbara Zobec Logar, 2017, original scientific article

Abstract: The aim of this retrospective single institution study was to analyse long term results of vulvar cancer treatment with conventional 2D radiotherapy in Slovenia between years 1997%2004. Patients and methods. Fifty-six patients, median age 74.4 years +/- 9.7 years, mainly stage T2 or T3, were included in the study. All patients were treated with radiotherapy, which was combined with surgery (group A), used as the primary treatment (group B) or at the time of relapse (group C). Chemotherapy was added in some patients. Histology, grade, lymph node status, details of surgery, radiation dose to the primary tumour, inguinofemoral and pelvic area as well as local control (LC) and survival were evaluated. Results. Overall survival (OS), disease specific survival (DSS) and LC rates at 10-years for all patients were as follows: 22.7%, 34.5% and 41.1%, respectively. The best 10-years results of the treatment were achieved in the primary operated patients treated with adjuvant radiotherapy +/-chemotherapy (OS 31.9%, DSS 40.6% and LC 47.6%). Positive lymph nodes had a strong influence on LC. In case of positive nodes LC decreased by 60% (p = 0.03) and survival decreased by 50% (p = 0.2). There was a trend to a better LC with higher doses % 54.0 Gy (p = 0.05). Conclusions. The best treatment option for patients with advanced vulvar cancer is combined treatment with surgery and radiotherapy +/- chemotherapy, if feasible. Radiotherapy with the dose of % 54.0 Gy should be considered to achieve better LC if positive adverse factors are present.
Keywords: vulvar cancer, radiotherapy, surgery, survival
Published in DiRROS: 31.05.2024; Views: 46; Downloads: 14
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Selection of non-small cell lung cancer patients for intercalated chemotherapy and tyrosine kinase inhibitors
Matjaž Zwitter, Antonio Rossi, Massimo Di Maio, Maja Pohar Perme, Gilberto Lopes, 2017, original scientific article

Abstract: Background. When treating patients with advanced non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors and chemotherapy, intercalated schedule with time separation between the two classes of drugs should avoid their mutual antagonism. In a survey of published trials, we focus on relation between eligibility criteria and effectiveness of intercalated treatment. Methods. Published documents were identified using major medical databases, conference proceedings and references of published trials. Median progression-free survival (PFS) was taken as the basic parameter of treatment efficacy. Correlation between characteristics of patients and median PFS was assessed through the Pearson%s correlation coefficient and the coefficient of determination, separately for first-line and second-line setting. Results. The series includes 11 single-arm trials and 18 randomized phase II or phase III trials with a total of 2903 patients. Treatment-naive patients or those in progression after first-line treatment were included in 16 and 13 trials, respectively. In 14 trials, only patients with non-squamous histology were eligible. Proportion of patients with nonsquamous carcinoma (in first-line setting), proportion of never-smokers (both in first- and second-line setting) and proportion of epidermal growth factor receptor (EGFR) mutant patients (both in first- and second-line setting) showed a moderate or strong correlation with median PFS. In six trials of intercalated treatment applied to treatment-naive EGFR%mutant patients, objective response was confirmed in 83.1% of cases and median PFS was 18.6 months. Conclusions. Most suitable candidates for intercalated treatment are treatment-naive patients with EGFR%mutant tumors, as determined from biopsy or liquid biopsy. For these patients, experience with intercalated treatment is most promising and randomized trials with comparison to the best standard treatment are warranted.
Keywords: lung cancer, NSCLC, intercalated treatment, EGFR, tyrosine -kinase inhibitors
Published in DiRROS: 31.05.2024; Views: 49; Downloads: 30
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Treatment-related cardiovascular toxicity in long-term survivors of testicular cancer
Jasenka Gugić Kevo, Lorna Zadravec-Zaletel, Irena Oblak, 2017, review article

Abstract: Testicular cancer is the most common malignancy in young men. Considering increasing incidence, exceptionally high cure rate, as well as long life expectancy, assessment of long term toxicity in testicular cancer survivors is of great importance. In the last decades a major effort has been made in order to reduce toxicity of treatment, while maintaining its high effectiveness. Conclusions Actual knowledge on treatment toxicity is based on outdated treatment modalities. Hopefully, modern treatment modalities could reduce toxicity, but, there is no firm confirmation for that at the moment, as data dealing with late sequelae of modern treatment of testicular cancer are not available yet due to the short period of observation. The life-threatening cardiovascular toxicity in testicular cancer survivors is major complication of platinum-based chemotherapy, mediastinal radiotherapy and even subdiaphragmatic radiotherapy.
Keywords: testicular cancer, cardiovascular toxicity, long-term survivors
Published in DiRROS: 24.05.2024; Views: 101; Downloads: 49
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Genetic counselling, BRCA1/2 status and clinico-pathologic characteristics of patients with ovarian cancer before 50 years of age
Mirjam Cvelbar, Marko Hočevar, Srdjan Novaković, Vida Stegel, Andraž Perhavec, Mateja Krajc, 2017, original scientific article

Abstract: In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we added also the data of previously genetically tested patients with EOC aged 45 to 49 years. Patients and methods. All clinical data have to be interpreted in the light of many changes happened in the field of EOC just in the last few years: new hystology stage classification (FIGO), new hystology types and differentiation grades classification, new therapeutic possibilities (PARP inhibitors available, also in Slovenia) and new guidelines for genetic counselling of EOC patients (National Comprehensive Cancer Network, NCCN), together with next-generation sequencing possibilities. Results. Compliance rate at the invitation was 43.1%. In the group of 27 invited or previously tested patients with EOC diagnosed before the age of 45 years, five gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within the group was 18.5%. There were 4 gBRCA1 and 1 gBRCA2 mutations detected. In the extended group of 42 tested patients with EOC diagnosed before the age of 50 years, 14 gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within this extended, partially selected group was 33.3%. There were 11 gBRCA1 and 3 gBRCA2 mutations detected. Conclusions. The rate of gBRCA1/2 mutation in tested unselected EOC patients under the age of 50 years was higher than 10%, namely 18.5%. Considering also a direct therapeuthic benefit of PARP inhibitors for BRCA positive patients, there is a double reason to offer genetic testing to all EOC patients younger than 50 years. Regarding clinical data, it is important to perform their re-interpretation in everyday clinical practice, because this may influence therapeutic possibilities to be offered.
Keywords: ovarian cancer, BRCA 1/2, genetic counseling
Published in DiRROS: 24.05.2024; Views: 100; Downloads: 49
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Cancer burden in Slovenia with the time trends analysis
Vesna Zadnik, Maja Primic-Žakelj, Katarina Lokar, Katja Jarm, Urška Ivanuš, Tina Žagar, 2017, original scientific article

Abstract: Background The aim of our study was to describe cancer burden and time trends of all cancers combined, the most frequent as well as the rare cancers in Slovenia. Patients and methods The principal data source was the population-based Cancer Registry of Republic of Slovenia. The cancer burden is presented by incidence and prevalence for the period 1950%2013 and by mortality for years 1985%2013. The time trends were characterized in terms of an average annual percent change estimated by the log-linear joinpoint regression. The Dyba-Hakulinen method was used for estimation of incidence in 2016 and the projections of cancer incidence for the year 2025 were calculated applying the Globocan projection software. Results In recent years, near 14,000 Slovenes were diagnosed with cancer per year and just over 6,000 died; more than 94,000 people who were ever diagnosed with cancer are currently living among us. The total burden of cancer is dominated by five most common cancer sites: skin (non-melanoma), colon and rectum, lung, breast and prostate, together representing almost 60% of all new cancer cases. On average the incidence of common cancers in Slovenia is increasing for 3.0% per year in last decade, but the incidence of rare cancers is stable. Conclusions Because cancer occurs more among the elderly, and additionally more numerous post-war generation is entering this age group, it is expected that the burden of this disease will be growing further, even if the level of risk factors remains the same as today.
Keywords: cancer burden, cancer registry, incidence, prevalence
Published in DiRROS: 24.05.2024; Views: 94; Downloads: 76
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Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence
Ana Lina Vodušek, Katja Goričar, Barbara Gazić, Vita Dolžan, Janez Jazbec, 2016, original scientific article

Abstract: Background. Thyroid cancer is one of the most common secondary cancers after treatment of malignancy in childhood or adolescence. Thyroid gland is very sensitive to the carcinogenic effect of ionizing radiation, especially in children. Imbalance between pro- and anti-oxidant factors may play a role in thyroid carcinogenesis. Our study aimed to assess the relationship between genetic variability of antioxidant defence-related genes and the risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence. Patients and methods. In a retrospective study, we compared patients with childhood or adolescence primary malignancy between 1960 and 2006 that developed a secondary thyroid cancer (cases) with patients (controls), with the same primary malignancy but did not develop any secondary cancer. They were matched for age, gender, primary diagnosis and treatment (especially radiotherapy) of primary malignancy. They were all genotyped for SOD2 p.Ala16Val, CAT c.-262C>T, GPX1 p.Pro200Leu, GSTP1 p.Ile105Val, GSTP1 p.Ala114Val and GSTM1 and GSTT1 deletions. The influence of polymorphisms on occurrence of secondary cancer was examined by McNemar test and Cox proportional hazards model. Results. Between 1960 and 2006 a total of 2641 patients were diagnosed with primary malignancy before the age of 21 years in Slovenia. Among them 155 developed a secondary cancer, 28 of which were secondary thyroid cancers. No significant differences in the genotype frequency distribution were observed between cases and controls. Additionally we observed no significant influence of investigated polymorphisms on time to the development of secondary thyroid cancer. Conclusions. We observed no association of polymorphisms in antioxidant genes with the risk for secondary thyroid cancer after treatment of malignancy in childhood or adolescence. However, thyroid cancer is one of the most common secondary cancers in patients treated for malignancy in childhood or adolescence and the lifelong follow up of these patients is of utmost importance.
Keywords: secondary thyroid cancer, antioxidant genes, genetic polymorphism
Published in DiRROS: 09.05.2024; Views: 105; Downloads: 64
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10.
CA19-9 serum levels predict micrometastases in patients with gastric cancer
Tomaž Jagrič, Stojan Potrč, Katarina Miš, Mojca Plankl, Tomaž Marš, 2016, original scientific article

Abstract: Background. We explored the prognostic value of the up-regulated carbohydrate antigen (CA19-9) in node-negative patients with gastric cancer as a surrogate marker for micrometastases. Patients and methods. Micrometastases were determined using reverse transcription quantitative polymerase chain reaction (RT-qPCR) for a subgroup of 30 node-negative patients. This group was used to determine the cut-off for preoperative CA19-9 serum levels as a surrogate marker for micrometastases. Then 187 node-negative T1 to T4 patients were selected to validate the predictive value of this CA19-9 threshold. Results. Patients with micrometastases had significantly higher preoperative CA19-9 serum levels compared to patients without micrometastases (p = 0.046). CA19-9 serum levels were significantly correlated with tumour site, tumour diameter, and perineural invasion. Although not reaching significance, subgroup analysis showed better five-year survival rates for patients with CA19-9 serum levels below the threshold, compared to patients with CA19-9 serum levels above the cut-off. The cumulative survival for T2 to T4 node-negative patients was significantly better with CA19-9 serum levels below the cut-off (p = 0.04). Conclusions. Preoperative CA19-9 serum levels can be used to predict higher risk for haematogenous spread and micrometastases in node-negative patients. However, CA19-9 serum levels lack the necessary sensitivity and specificity to reliably predict micrometastases.
Keywords: gastric cancer, micrometastases, CA19-9, rak (medicina), želodec, metastaze, diagnostika, antigeni, tumorski označevalci
Published in DiRROS: 09.05.2024; Views: 102; Downloads: 77
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