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1.
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: 35; Downloads: 21
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Susceptibility of X17CrNi16-2 martensitic stainless steel to hydrogen embrittlement after conventional and deep cryogenic heat treatment
Mirjam Bajt Leban, Bojan Zajec, Bojan Podgornik, Črtomir Donik, Patricia Jovičević Klug, Miha Hren, Andraž Legat, 2024, original scientific article

Abstract: A low carbon/ high chromium martensitic stainless steel, X17CrNi16-2, was heat treated using two different hardening and tempering regimes (1050 ◦ C/480 ◦ C or 980 ◦C/600 ◦C) — promoting either a high strength or high toughness state, respectively and further combined with deep cryogenic treatment (DCT) at 196 ◦C for 24 h. Over recent years DCT has been recognized as a promising technique to improve the properties of steel, predominantly with respect to its tensile strength, toughness and wear resistance. The influence of DCT on the hydrogen embrittlement resistance of martensitic stainless steel has not yet, however, been reported. A slow strain rate tensile test (SSRT) with simultaneous cathodic hydrogen charging was selected as the method to assess potential susceptibility to hydrogen embrittlement (HE). Relatively low-intensity hydrogen charging, utilizing a constant current density of 0.1 mA/cm2, in a non-corrosive, slightly alkaline buffer solution, led to a clear reduction in the ultimate tensile stress. This reduction, and therefore the HE susceptibility, was more pronounced in the steel with a higher strength (i.e. that subject to the 1050 ◦C/ 480 ◦C heat treatment condition). Furthermore, DCT did not appear to have any impact on the steel’s mechanical properties in the presence of hydrogen. Fractographic analysis showed clear evidence of HE in the hydrogen-charged specimens. This paper presents results of the SSRT tests and further fractography results, and discusses the impact of conventional and deep cryogenic treatment on HE susceptibility.
Keywords: martensitic stainless steel, deep cryogenic treatment, hydrogen embrittlement, slow strain rate tensile test
Published in DiRROS: 23.05.2024; Views: 86; Downloads: 86
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Malignant gliomas : old and new systemic treatment approaches
Tanja Mesti, Janja Ocvirk, 2016, review article

Abstract: Malignant (high-grade) gliomas are rapidly progressive brain tumours with very high morbidity and mortality. Until recently, treatment options for patients with malignant gliomas were limited and mainly the same for all subtypes of malignant gliomas. The treatment included surgery and radiotherapy. Chemotherapy used as an adjuvant treatment or at recurrence had a marginal role. Conclusions. Nowadays, the treatment of malignant gliomas requires a multidisciplinary approach. The treatment includes surgery, radiotherapy and chemotherapy. The chosen approach is more complex and individually adjusted. By that, the effect on the survival and quality of life is notable higher.
Keywords: malignant gliomas, systemic treatment, multidisciplinary, survival
Published in DiRROS: 30.04.2024; Views: 176; Downloads: 41
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Immunotoxin - a new treatment option in patients with relapsed and refractory Hodgkin lymphoma
Barbara Jezeršek Novaković, 2015, review article

Abstract: Background. Even though Hodgkin lymphoma is a highly curable disease, some of the patients have either a refractory disease or experience a relapse following a successful primary therapy. Durable responses and remissions in patients with relapsed or refractory disease may be achieved in approximately one-half with salvage chemotherapy followed by high dose chemotherapy (HDT) and autologous hematopoietic cell rescue (SCT). On the other hand, patients who relapse after HDT and autologous SCT or those who have failed at least two prior multi-agent chemotherapy regimens and are not candidates for HDT have limited treatment options. Conclusions. A new treatment option in this population is an immunotoxin Brentuximab vedotin composed of a CD30 directed antibody linked to the antitubulin agent monomethyl auristatin E. It has demonstrated a substantial effectiveness and an acceptable toxicity. In the pivotal study, the overall response rate was 75% with 34% of complete remissions. The median durations of response were 20.5 and 6.7 months for those with complete remission and all responding patients, respectively. The median overall survival was 40.5 months (3-years overall survival 54%) and the median progression-free survival 9.3 months. The most common non-hematologic toxicities were peripheral sensory neuropathy, nausea, and fatigue while the most common severe side effects were neutropenia, thrombocytopenia, anemia, and peripheral sensory neuropathy.
Keywords: immunotoxin, Hodgkin lymphoma, toxicity, new treatment option
Published in DiRROS: 22.04.2024; Views: 392; Downloads: 389
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Aggressive anticancer treatment in the last 2 weeks of life
Nena Golob, Teja Oblak, Luka Čavka, Maša Kušar, Boštjan Šeruga, 2024, original scientific article

Abstract: Background: There is a concern that terminally ill cancer patients may be aggressively treated due to the rapidly growing possibilities of anticancer treatment. The aim of this study was to evaluate the use of anticancer treatment at the end of life (EoL). Materials and methods: This retrospective study included adult patients with advanced solid cancers who were treated at the Institute of Oncology Ljubljana and died of cancer between January 2015 and December 2019. A multiple logistic regression model was used to assess an association between the aggressiveness of anticancer treatment (i.e. systemic therapy, radiotherapy and surgery) in the last 2 weeks of life and year of death, age at death, sex, prognosis of cancer and enrolment into the specialist palliative care (SPC). Results: We included 1736 patients in our analysis. Overall, 13.7% of patients were enrolled into the SPC and 14.4% received anticancer treatment in the last 2 weeks of life. The odds of receiving anticancer treatment significantly increased over time [odds ratio (OR) 1.15, 95% confidence interval (CI) 1.04-1.27]. There was an increased use of novel systemic therapy (e.g. small-molecule targeted therapy and immunotherapy) at the EoL. Older patients had significantly lower odds to receive anticancer treatment in the last 2 weeks of life as compared to younger patients (OR 0.96, 95% CI 0.95-0.98). As compared to patients receiving only a standard oncology care, those also enrolled into the SPC had significantly lower odds for anticancer treatment in the last 2 weeks of life (OR 0.22, 95% CI 0.12-0.43). Conclusions: Terminally ill cancer patients have increased odds for receiving anticancer treatment, especially novel systemic therapies, in the last 2 weeks of life. Younger patients and those not enrolled into the SPC are at particular risk for anticancer treatment at the EoL
Keywords: systemic therapy, aggressive treatment, anticancer drugs, palliative care
Published in DiRROS: 18.04.2024; Views: 142; Downloads: 74
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The cost of systemic therapy for metastatic colorectal carcinoma in Slovenia : discrepancy analysis between cost and reimbursement
Tanja Mesti, Biljana Mileva Boshkoska, Mitja Kos, Metka Tekavčič, Janja Ocvirk, 2015, original scientific article

Abstract: The aim of the study was to estimate the direct medical costs of metastatic colorectal cancer (mCRC) treated at the Institute of Oncology Ljubljana and to question the healthcare payment system in Slovenia. Methods. Using an internal patient database, the costs of mCRC patients were estimated in 2009 by examining (1) mCRC direct medical related costs, and (2) the cost difference between payment received by Slovenian health insurance and actual mCRC costs. Costs were analysed in the treatment phase of the disease by assessing the direct medical costs of hospital treatment with systemic therapy together with hospital treatment of side effects, without assessing radiotherapy or surgical treatment. Follow-up costs, indirect medical costs, and nonmedical costs were not included. Results. A total of 209 mCRC patients met all eligibility criteria. The direct medical costs of mCRC hospitalization with systemic therapy in Slovenia for 2009 were estimated as the cost of medications (cost of systemic therapy + cost of drugs for premedication) + labor cost (the cost of carrying out systemic treatment) + cost of lab tests + cost of imaging tests + KRAS testing cost + cost of hospital treatment due to side effects of mCRC treatment, and amounted to %3,914,697. The difference between the cost paid by health insurance and actual costs, estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009, was %1,900,757.80. Conclusions. The costs paid to the Institute of Oncology Ljubljana by health insurance for treating mCRC with systemic therapy do not match the actual cost of treatment. In fact, the difference between the payment and the actual cost estimated as direct medical costs of hospitalization of mCRC patients treated with systemic therapy at the Institute of Oncology Ljubljana in 2009 was %1,900,757.80. The model Australian Refined Diagnosis Related Groups (AR-DRG) for cost assessment in oncology being currently used is probably one of the reasons for the discrepancy between pay-outs and actual costs. We propose new method for more precise cost assessment in oncology.
Keywords: cost of treatment, metastatic colorectal cancer, cost of targeted therapy, monitoring costs
Published in DiRROS: 17.04.2024; Views: 187; Downloads: 48
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