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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: 30.10.2017; Views: 623; Downloads: 213
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Hypodontia prevalence and pattern in women with epithelial ovarian cancer
Anita Fekonja, Andrej Čretnik, Iztok Takač, 2014, original scientific article

Abstract: Objective: To analyze the possible association between hypodontia and epithelial ovarian cancer (EOC), with the special interest in hypodontia pattern. Materials and Methods: One hundred twenty women with EOC treated at the Department of Gynecologic and Breast Oncology at the University Clinical Centre and 120 gynecologically healthy women of the same average age were reviewed for the presence and pattern of hypodontia. Collected data were analyzed for frequency, tooth type, location per jaw and side, number of missing teeth per person, and family history of hypodontia. Results: The results of the study showed prevalence of hypodontia in 19.2% of women with EOC and in 6.7% of women in the control group (P = .004). The most frequently missing teeth for women with EOC and women in the control group were maxillary second premolars and maxillary lateral incisors, respectively. Unilateral occurrence of hypodontia was more common than bilateral occurrence in women with EOC (P = .034). Of women with EOC and hypodontia, 21.7% reported a positive family history of hypodontia compared with no report in the control group of women with hypodontia (P = .150). Conclusions: The results statistically support possible association between EOC and hypodontia. Because hypdontia can be recognized early in life, this finding could possibly help in earlier detection of EOC, resulting in better prognosis and treatment in earlier stages of the disease. Earlier EOC diagnosis and treatment could save many lives.
Keywords: hypodontia, tooth agenesis, ovarian cancer, neoplasms
Published: 07.08.2017; Views: 617; Downloads: 259
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Low-dose gemcitabine in long infusion
Matjaž Zwitter, 2012, short scientific article

Keywords: lung cancer, gemcitabine
Published: 04.08.2017; Views: 550; Downloads: 55
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Independent clinical research may alleviate disparities in cancer treatment
Matjaž Zwitter, 2016, original scientific article

Abstract: Disparities in cancer care are a reality of the modern world. Unfortunately, current clinical research is in the hands of for-profit pharmaceutical companies and of researchers from the developed world. Problems specific to cancer care in developing countries and among deprivileged populations are ignored. Independent clinical research can offer new valuable knowledge and identify affordable and cost-effective treatments. As such, research not depending on commercial sponsors should become one of the important avenues to alleviate the problem of cancer disparities.
Keywords: clinical research, disparities in cancer care, cost-effective treatment
Published: 04.08.2017; Views: 690; Downloads: 262
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TMPRSS2:ERG gene aberrations may provide insight into pT stage in prostate cancer
Zoran Krstanoski, Nadja Kokalj-Vokač, Andreja Zagorac, Boris Pospihalj, Miha Munda, Sašo Džeroski, Rastko Golouh, 2016, original scientific article

Abstract: Background: TMPRSS2:ERG gene aberration may be a novel marker that improves risk stratification of prostate cancer before definitive cancer therapy, but studies have been inconclusive. Methods: The study cohort consisted of 202 operable prostate cancer Slovenian patients who underwent laparoscopic radical prostatectomy. We retrospectively constructed tissue microarrays of their prostatic specimens for fluorescence in situ hybridization, with appropriate signals obtained in 148 patients for subsequent statistical analyses. Results: The following genetic aberrations were found: TMPRSS2:ERG fusion, TMPRSS2 split (a non-ERG translocation) and ERG split (an ERG translocation without involvement of TMPRSS2). TMPRSS2:ERG gene fusion happened in 63 patients (42 %), TMPRSS2 split in 12 patients and ERG split in 8 patients. Association was tested between TMPRSS2:ERG gene fusion and several clinicopathological variables, i.e., pT stage, extended lymph node dissection status, and Gleason score, correcting for multiple comparisons. Only the association with pT stage was significant at p = 0.05: Of 62 patients with pT3 stage, 34 (55 %) had TMPRSS2:ERG gene fusion. In pT3 stage patients, stronger (but not significant) association between eLND status and TMPRSS2:ERG gene fusion was detected. We detected TMPRSS2:ERG gene fusion in 64 % of the pT3 stage patients where we did not perform an extended lymph node dissection. Conclusions: Our results indicate that it is possible to predict pT3 stage at final histology from TMPRSS2:ERG gene fusion at initial core needle biopsy. FISH determination of TMPRSS2:ERG gene fusion may be particularly useful for patients scheduled to undergo a radical prostatectomy in order to improve oncological and functional results.
Keywords: FISH, predicting pT stage, radical prostatectomy, prostate cancer, TMPRSS2:ERG fusion
Published: 29.06.2017; Views: 815; Downloads: 312
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Survival of node-negative breast cancer patients treated at the University Medical Centre Maribor in the period 2000-2009
Nina Fokter Dovnik, Darja Arko, Nina Čas-Sikošek, Iztok Takač, 2017, original scientific article

Abstract: Introduction: Breast cancer is increasingly diagnosed in the early stages without regional nodal involvement. The aim of the present study was to determine the 5-year overall (OS) and breast cancer specific survival (BCSS) for patients with node-negative breast cancer treated at the University Medical Centre Maribor, and compare it with survival at the national level. Methods: Medical records were searched for information on patients with lymph node-negative invasive breast cancer who received primary treatment at the University Medical Centre Maribor in the period 2000–2009. Information on all Slovenian node-negative breast cancer patients diagnosed in the same period was obtained from the Cancer Registry of Republic of Slovenia. Time trends in survival were assessed by comparing the periods 2000–2004 and 2005–2009. Results: The 5-year OS and BCSS of patients treated in Maribor in the period 2000–2009 were 92.3% (95% CI, 90.5%– 94.1%) and 96.4% (95% CI, 95.2%–97.6%), respectively, and did not differ from the corresponding OS and BCSS for Slovenian patients. Although the improvement in OS for patients from Maribor diagnosed in the period 2005–2009 compared to 2000–2004 did not reach statistical significance (HR 0.73; 95% CI, 0.51–1.05; p=0.086), BCSS significantly improved over the same time periods (HR 0.53; 95% CI, 0.30–0.94; p=0.028). Conclusions: Survival of node-negative breast cancer patients treated at the University Medical Centre Maribor is comparable to survival of corresponding patients at the national level. The rising number of long-term breast cancer survivors places additional importance on survivorship care.
Keywords: breast cancer, survival, time trends, regional differences, Slovenia
Published: 26.06.2017; Views: 642; Downloads: 271
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Skin cancer and its treatment
Kristjan Orthaber, Matevž Pristovnik, Kristijan Skok, Barbara Perić, Uroš Maver, 2017, review article

Abstract: The life expectancy in the Western world is increasing for a long time, which is the courtesy of a higher life standard, a more thorough hygiene, and, of course, the progress of modern medicine. Nevertheless, one of the illnesses that still proves to be a great challenge regardless of the recent advancements in medicine is cancer. Skin cancer is, according to theWorld Health Organization, the most common malignancy for the white population.The beginning of the paper offers a brief overview of the latest available information concerning epidemiology, aetiology, diagnostics, and treatment options for skin cancer, whereas the rest of the article deals with modern approaches to skin cancer treatment, highlighting recent development of nanotechnology based treatment approaches. Among these, we focus especially on the newest nanotechnological approaches combined with chemotherapy, a field which specialises in target specificity, drug release control, and real time monitoring with the goal being to diminish unwanted side effects and their severity, achieving a cheaper treatment and a generally more efficient chemotherapy. The field of nanotechnology is a rapidly developing one, judging by already approved clinical studies or by new theranostic agents that combine both the therapeutic and diagnostic modalities.
Keywords: skin cancer, treatment, nanotechnology, nanotechnological methods
Published: 14.06.2017; Views: 501; Downloads: 63
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Intermittent chemotherapy and erlotinib for nonsmokers or light smokers with advanced adenocarcinoma of the lung
Matjaž Zwitter, Mirjana Rajer, Viljem Kovač, Izidor Kern, Martina Vrankar, Uroš Smrdel, 2011, original scientific article

Abstract: Background. Intermittent application of chemotherapy and tyrosine kinase inhibitors may avoid antagonism between the two classes of drugs. This hypothesis was tested in a Phase II clinical trial. Patients and Methods. Eligible patients were nonsmokers or light smokers, chemo-naïve, with metastatic adenocarcinoma of the lung. Treatment: 4 to 6 cycles of gemcitabine 1250 mg/m2 on days 1 and 4, cisplatin 75 mg/m2 on day 2, and erlotnib 150 mg daily on days 5–15, followed by erlotinib as maintenance. Results. 24 patients entered the trial. Four pts had grade 3 toxicity. Complete remission (CR) and partial remission (PR) were seen in 5 pts and 9 pts, respectively (response rate 58%). Median time to progression (TTP) was 13.4 months and median overall survival (OS) was 23 months. When compared to patients with negative or unknown status of EGFR mutations, 8 patients with EGFR gene activating mutations had significantly superior experience: 4 CR and 4 PR, with median TTP 21.5 months and OS 24.2 months (P < .05). Conclusions. Intermittent schedule with gemcitabine, cisplatin and erlotinib has mild toxicity. For patients who are positive for EGFR gene activating mutations, this treatment offers excellent response rate, time to progression and survival.
Keywords: smokers, nonsmokers, cancer treatment, lung cancer, chemotherapy, erlotinib
Published: 14.06.2017; Views: 611; Downloads: 78
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Single nucleotide polymorphisms as prognostic and predictive factors of adjuvant chemotherapy in colorectal cancer of stages I and II
Matej Horvat, Uroš Potočnik, Katja Repnik, Rajko Kavalar, Borut Štabuc, 2016, review article

Abstract: Colorectal cancer (CRC) is a highly heterogeneous disease regarding the stage at time of diagnosis and there is special attention regarding adjuvant chemotherapy in unselected patients with stage I and stage II. The clinicohistologically based TNM staging system with emphasis on histological evaluation of primary tumor and resected regional lymph nodes remains the standard of staging, but it has restricted sensitivity resulting in false downward stage migration. Molecular characteristics might predispose tumors to a worse prognosis and identification of those enables identifying patients with high risk of disease recurrence. Suitable predictive markers also enable choosing the most appropriate therapy. The current challenge facing adjuvant chemotherapy in stages I and II CRC is choosing patients with the highest risk of disease recurrence who are going to derive most benefit without facing unnecessary adverse effects. Single nucleotide polymorphisms (SNPs) are one of the potential molecular markers that might help us identify patients with unfavorable prognostic factors regarding disease initiation and recurrence and could determine selection of an appropriate chemotherapy regimen in the adjuvant and metastatic setting. In this paper, we discuss SNPs of genes involved in the multistep processes of cancerogenesis, metastasis, and the metabolism of chemotherapy that might prove clinically significant.
Keywords: single nucleotide polymorphism, colorectal cancer, adjuvant chemotherapy
Published: 14.06.2017; Views: 543; Downloads: 270
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Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients
Nina Fokter Dovnik, Iztok Takač, 2017, original scientific article

Abstract: Background: The association of HER2 status with urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) levels raises the question whether uPA/PAI-1 level carries additional clinically relevant prognostic information independently from HER2 status. The aim of our study was to compare the prognostic value of uPA/PAI-1 level, HER2 status, and traditional prognostic factors for survival in node-negative breast cancer patients. Patients and methods: A retrospective analysis of 858 node-negative breast cancer patients treated in Maribor University Clinical Center, Slovenia, in the years 2000-2009 was performed. Data were obtained from patient medical records. The median follow-up time was 100 months. Univariate and multivariate analyses of disease-free (DFS) and overall survival (OS) were performed using the Cox regression and the Cox proportional hazards model. Results: In univariate analysis, age, tumor size, grade, lymphovascular invasion, HER2 status and UPA/PAI-1 level were associated with DFS, and age, tumor size, grade, and uPA/PAI-1 level were associated with OS. In the multivariate model, the most important determinants of DFS were age, estrogen receptor status and uPA/PAI-1 level, and the most important factors for OS were patient age and tumor grade. The HR for death from any cause in the multivariate model was 1.98 (95% CI 0.83-4.76) for patients with high uPA and/or PAI-1 compared to patients with both values low. Conclusions: uPA/PAI-1 level clearly carries an independent prognostic value regardless of HER2 status in node-negative breast cancer and could be used in addition to HER2 and other markers to guide clinical decisions in this setting.
Keywords: node-negative breast cancer, adjuvant systemic treatment, survival, uPA/PAI-1, HER2 status
Published: 10.05.2017; Views: 642; Downloads: 305
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