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Open access

Brigita Gregoric, Vesna Zadnik and Barbara Novakovic

The diffuse large B-cell lymphoma - where do we stand now in everyday clinical practice

Background. Due to superior results observed with the addition of rituximab into treatment of patients with the diffuse large B-cell lymphoma (DLBCL), the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen and its variants became the standard initial treatment of these patients. However, the treatment recommendations are based on results of clinical studies while the conditions of routine treatment are far different from the ones in clinical studies. The aim of this retrospective study was therefore to compare the treatment results of routinely treated patients with the DLBCL to results reported by some larger studies.

Patients and methods. Two hundred and ninety five patients with the DLBCL were treated between 2004 and 2008 according to the then protocol with R-CHOP or R-CHOP-like regimens at the Institute of Oncology Ljubljana. Treatment response was evaluated according to Cheson's criteria and the disease-free and overall survival by means of Kaplan Meier survival curves.

Results. Response to treatment in our evaluation diverged from the reported one predominately in the low risk group (international prognostic index [IPI] categorisation) and in the very good prognosis group (revised international prognostic index (R-IPI) categorisation). The determined complete response (CR) rates in other IPI and R-IPI groups were generally within expectations. Also in the disease-free survival the largest discrepancy occurred in the low-risk patient group (3 year disease-free survival rate of 75%) and in the very good prognosis group (4 year disease-free survival rate of 59%). In all other IPI risk groups, the disease-free survival at 3 years (low intermediate risk 76%, high intermediate risk group 57%, and high risk group 53%) agreed very well with the quoted ones. Slightly worse was the compliance of the 4 year disease-free survival rates (72% in the good prognosis and 51% in the poor prognosis group) with the results from the literature. The 3 year overall survival rates (low risk patients 87%, high intermediate risk 61% and high risk patients 51%) were somewhat worse than the reported ones in all IPI subgroups except in the low intermediate risk group (82%). On the other hand, the 4 year overall survival rates of the R-IPI categories (94% in the very good prognosis group, 80% in the good prognosis group, 56% in the poor prognosis group) were much better correlated with the data from the literature.

Conclusions. In total, the treatment outcomes of routinely treated patient with the DLBCL at our institute are quite encouraging when compared to results of some larger studies. There are probably no dilemmas about how to treat young good prognosis patients and patients aged over 60 years at present. However, the 5 year overall survival rate of 76% for the young poor prognosis group is unsatisfying and needs to be improved. At present, quite a few studies are underway to clarify which of the regimens will perform best in this population.

Open access

Vesna Zadnik and Mateja Krajc

Abstract

The incidence of hormone-related cancers tends to be higher in the developed world than in other countries. In Slovenia, six hormone-related cancers (breast, ovarian, endometrial, prostate, testicular, and thyroid) account for a quarter of all cancers. Their incidence goes up each year, breast and prostate cancer in particular. The age at diagnosis is not decreasing for any of the analysed cancer types. The risk of breast cancer is higher in the western part of the country, but no differences in geographical distribution have been observed for other hormone-related cancers. Furthermore, areas polluted with endocrine-disrupting chemicals that affect hormone balance such as PCBs, dioxins, heavy metals, and pesticides, do not seem to involve a greater cancer risk. We know little about how many cancers can be associated with endocrine disruptors, as there are too few reliable exposure studies to support an association.

Open access

Nebojsa Glumac, Marko Hocevar, Vesna Zadnik and Marko Snoj

Inguinal or inguino-iliac/obturator lymph node dissection after positive inguinal sentinel lymph node in patients with cutaneous melanoma

Background. The aim of the study was to determine whether the presence of inguinal sentinel lymph node (SLN) metastases smaller than 2 mm (micrometastases) subdivided according to the number of micrometastases predicts additional, non-sentinel inguinal, iliac or obturator lymph node involvement in completion lymph node dissection (CLND).

Patients and methods. Positive inguinal SLN was detected in 58 patients (32 female, 26 male, median age 55 years) from 743 consecutive and prospectively enrolled patients with primary cutaneous melanoma stage I and II who were treated with SLN biopsy between 2001 and 2007.

Results. Micrometastases in inguinal SLN were detected in 32 patients, 14 were single, 2 were double, and 16 were multiple. Twenty-six patients had macrometastases.

Conclusions. No patient with any micrometastases or a single SLN macrometastasis in the inguinal region had any iliac/obturator non-sentinel metastases after CLND in our series. Furthermore, no patient with single SLN micrometastasis in the inguinal region had any non-sentinel metastases at all after CLND in our series. In these cases respective CLND might be omitted.

Open access

Vesna Zadnik, Tina Žagar and Maja Primic Žakelj

Abstract

Background

Cancer patients’ survival is an extremely important but complex indicator for assessing regional or global inequalities in diagnosis practices and clinical management of cancer patients. The population-based cancer survival comparisons are available through international projects (i.e. CONCORD, EUROCARE, OECD Health Reports) and online systems (SEER, NORDCAN, SLORA). In our research we aimed to show that noticeable differences in cancer patients’ survival may not always reflect the real inequalities in cancer care, but can also appear due to variations in the applied methodology for relative survival calculation.

Methods

Four different approaches for relative survival calculation (cohort, complete, period and hybrid) have been implemented on the data set of Slovenian breast cancer patients diagnosed between 2000 and 2009, and the differences in survival estimates have been quantified. The major cancer survival comparison studies have been reviewed according to the selected relative survival calculation approach.

Results

The gap between four survival curves widens with time; after ten years of follow up the difference increases to more than 10 percent points between the highest (hybrid) and the lowest (cohort) estimates. In population-based comparison studies, the choice of the calculation approach is not uniformed; we noticed a tendency of simply using the approach which yields numerically better survival estimates.

Conclusion

The population-based cancer relative survival, which is continually reported by recognised research groups, could not be compared directly as the methodology is different, and, consequently, final country scores differ. A uniform survival measure would be of great benefit in the cancer care surveillance.

Open access

Luka Vitez, Petra Zupet, Vesna Zadnik and Matej Drobnič

Abstract

Introduction

The aim of our study was to determine the self-reported incidence and prevalence of running-related injuries among participants of the 18th Ljubljana Marathon, and to identify risk factors for their occurrence.

Methods

A customized questionnaire was distributed over registration. Independent samples of t-test and chi-square test were used to calculate the differences in risk factors occurrence in the injured and non-injured group. Factors which appeared significantly more frequently in the injured group were included further into multiple logistic regression analysis.

Results

The reported lifetime running injury (absence >2 weeks) incidence was: 46% none, 47% rarely, 4% occasionally, and 2% often. Most commonly injured body regions were: knee (30%), ankle and Achilles’ tendon (24%), foot (15%), and calf (12%). Male gender, running history of 1-3 years, and history of previous injuries were risk factors for life-time running injury. In the season preceding the event, 65% of participants had not experienced any running injuries, 19% of them reported minor problems (max 2 weeks absenteeism), but 10% and 7% suffered from moderate (absence 3-4 weeks) or major (more than 4 weeks pause) injuries. BMI was identified as the solely risk factor.

Conclusions

This self-reported study revealed a 53% lifetime prevalence of running-related injuries, with the predominate involvement of knee, ankle and Achilles’ tendon. One out of three recreational runners experienced at least one minor running injury per season. It seems that male gender, short running experience, previous injury, and BMI do increase the probability for running-related injuries.

Open access

Vaneja Velenik, Ajra Secerov-Ermenc, Jasna But-Hadzic and Vesna Zadnik

Abstract

Background

The aim of our study was to obtain reference data of the EORTC QLQ-C30 quality of life dimensions for the general Slovenian population. We intend to provide the researchers and clinicians in our country with the expected mean health-related quality of life (HRQL) scores for distinctive socio-demographic population groups.

Methods

The EORTC QLQ-C30 questionnaire supplemented by a socio-demographic inquiry was mailed or distributed to 1,685 randomly selected individuals in the Slovenian population aged 18 – 90. Answers from 1,231 subjects representing socio-demographic diversity of the Slovenian population were collected and transformed into EORTC dimensions and symptoms. The impact of socio-demographic features on HRQL scores was assessed by multiple linear regression models.

Results

Gender, age and self-rated social class are the important confounders in the quality of life scores in our population. Men reported better quality of life on the majority of the specific scales and, at the same time, reported fewer symptoms. There was no gender-specific difference in cognitive functioning. The mean scores were consistently lower with age in both sexes.

Conclusions

This is the first study to report the normative EORTC QLQ-C30 scores for one of the south-eastern European populations. The reported expected mean scores allow Slovenian oncologists to estimate what the quality of life in cancer patients would be, had they not been ill. As they are derived by common methodology, our results can easily be included in any further international comparisons or in the calculation of European summarized HRQL scores.

Open access

Mirta Kozelj, Samo Zver and Vesna Zadnik

Background. Tandem autologous hematopoietic stem cell transplantation (ta-HSCT) is a standard treatment for multiple myeloma (MM). Patients receive a high-dose cyclophosphamide (CY), followed by two myeloablative cycles of melphalan (MEL). There are scarce data about long term cardiotoxicity.

Patients and methods. We studied 12 patients (62.25 ± 8.55 years) six years after the completion of MM treatment with ta-HCST. Late cardiotoxic effects were evaluated clinically and echocardiographically.

Results. None of the patients developed clinical signs of heart failure, all were in sinus rhythm and NT-pro BNP concentration was elevated (778 ± 902.76 pg/mL). The left ventricular (LV) size remained normal. The LV ejection fraction did not decrease (73.75 ± 5.67%, 69.27 ± 6.13%, p = NS). The LV diastolic function parameters (E, A, ratio E/A and A/a) did not change significantly. In tissue Doppler parameters we observed a nonsignificant decrease in Em (10.26 ± 2.63 cm/s, 7.57 ± 1.43 cm/s) and Sm velocities (8.7 ± 0.87 cm/s, 7.14 ± 1.17 cm/s, p = NS). The E/Em values were in an abnormal range (8.66 ± 1.05, 10.55 ± 2.03).

Conclusions. The treatment of MM with ta-HSCT, during which patients receive a high dose CY followed by two myeloablative cycles of MEL, causes mild, chronic, partially reversible and clinically silent cardiotoxic side-effects. However, ta-HSCT in patients with MM is a safe regarding cardiotoxic side effects, but, because of increasing life expectancy needs long term attention.

Open access

Matej Horvat, Uros Potocnik, Katja Repnik, Rajko Kavalar, Vesna Zadnik, Stojan Potrc and Borut Stabuc

Abstract

Background

Colorectal cancer (CRC) represents one of the most common malignancies worldwide. Research has indicated that functional gene changes such as single nucleotide polymorphism (SNP) influence carcinogenesis and metastasis and might have an influence on disease relapse. The aim of our study was to evaluate the role of SNPs in selected genes as prognostic markers in resectable CRC.

Patients and methods

In total, 163 consecutive patients treated surgically for CRC of stages I, II and III at the University Medical Centre in Maribor in 2007 and 2008 were investigated. DNA was isolated from formalin-fixed paraffin-embedded CRC tissue from the Department of Pathology and SNPs in genes SDF-1a, MMP7, RAD18 and MACC1 were genotyped using polymerase chain reaction followed by high resolution melting curve analysis or restriction fragment length polymorphism.

Results

We found worse disease-free survival (DFS) for patients with TT genotype of SNP rs1990172 in gene MACC1 (p = 0.029). Next, we found worse DFS for patients with GG genotype for SNP rs373572 in gene RAD18 (p = 0.020). Higher frequency of genotype GG of MMP7 SNP rs11568818 was found in patients with T3/T4 stage (p = 0.014), N1/N2 stage (p = 0.041) and with lymphovascular invasion (p = 0.018). For MACC1 rs1990172 SNP we found higher frequency of genotype TT in patients with T3/T4 staging (p = 0.024). Higher frequency of genotype GG of RAD18 rs373572 was also found in patients with T1/T2 stage with disease relapse (p = 0.041).

Conclusions

Our results indicate the role of SNPs as prognostic factors in resectable CRC.

Open access

Vesna Zadnik, Elodie Guillaume, Katarina Lokar, Tina Žagar, Maja Primic Žakelj, Guy Launoy and Ludivine Launay

Abstract

Introduction

Ecological deprivation indices belong to essential instruments for monitoring and understanding health inequalities. Our aim was to develop the SI-EDI, a newly derived European Deprivation Index for Slovenia. We intend to provide researchers and policy-makers in our country with a relevant tool for measuring and reducing the socioeconomic inequalities in health, and even at a broader level.

Methods

Data from the European survey on Income and Living Conditions and Slovenian national census for the year 2011 were used in the SI-EDI construction. The concept of relative deprivation was used where deprivation refers to unmet need(s), which is caused by lack of all kinds of resources, not only material. The SI-EDI was constructed for 210 Slovenian municipalities. Its geographical distribution was compared to the distribution of two existing deprivation scores previously applied in health inequality research in Slovenia.

Results

There were 36% of adults recognized as deprived in Slovenia in 2011. SI-EDI was calculated using 10 census variables that were associated with individual deprivation. A clear east-to-west gradient was detected with the most deprived municipalities in the eastern part of the country. The two existing deprivation scores correlate significantly with the SI-EDI.

Conclusions

A new deprivation index, the SI-EDI, is grounded on the internationally established scientific concept, can be replicated over time and, crucially, provides an account of the socioeconomic and cultural particularities of the Slovenian population. The SI-EDI could be used by the stakeholders and the governmental and nongovernmental sectors in Slovenia, with the goal of better understanding health inequalities in Slovenia.

Open access

Maja Ebert Moltara, Srdjan Novakovic, Marko Boc, Marina Bucic, Martina Rebersek, Vesna Zadnik and Janja Ocvirk

Abstract

Background

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.