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3. Bevacizumab and irinotecan in recurrent malignant glioma, a single institution experienceTanja Mesti, Maja Ebert Moltara, Marko Boc, Martina Reberšek, Janja Ocvirk, 2015, original scientific article Abstract: Treatment options of recurrent malignant gliomas are very limited and with a poor survival benefit. The results from phase II trials suggest that the combination of bevacizumab and irinotecan is beneficial. Patients and methods. The medical documentation of 19 adult patients with recurrent malignant gliomas was retrospectively reviewed. All patients received bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 or 125 mg/m2) every two weeks. Patient clinical characteristics, drug toxicities, response rate, progression free survival (PFS) and overall survival (OS) were evaluated. Results. Between August 2008 and November 2011, 19 patients with recurrent malignant gliomas (median age 44.7, male 73.7%, WHO performance status 0%2) were treated with bevacizumab/irinotecan regimen. Thirteen patients had glioblastoma, 5 anaplastic astrocytoma and 1 anaplastic oligoastrocytoma. With exception of one patient, all patients had initially a standard therapy with primary resection followed by postoperative chemoradiotherapy. Radiological response was confirmed after 3 months in 9 patients (1 complete response, 8 partial responses), seven patients had stable disease and three patients have progressed. The median PFS was 6.8 months (95% confidence interval [CI]: 5.3-8.3) with six-month PFS rate 52.6%. The median OS was 7.7 months (95% CI: 6.6-8.7), while six-month and twelve-month survival rates were 68.4% and 31.6%, respectively. There were 16 cases of hematopoietic toxicity grade (G) 1-2. Non-hematopoietic toxicity was present in 14 cases, all G1-2, except for one patient with proteinuria G3. No grade 4 toxicities, no thromboembolic event and no intracranial hemorrhage were observed. Conclusions. In recurrent malignant gliomas combination of bevacizumab and irinotecan might be an active regimen with acceptable toxicity.
Keywords: recurrent malignant glioma, systemic therapy, bevacizumab
Published in DiRROS: 17.04.2024; Views: 48; Downloads: 7
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4. Intercalated chemotherapy and erlotinib for advanced NSCLC : high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutationsMatjaž Zwitter, Karmen Stanič, Mirjana Rajer, Izidor Kern, Martina Vrankar, Natalija Edelbaher, Viljem Kovač, 2014, original scientific article Abstract: Background. Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC). Patients and methods. Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance. Results. Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2%3 (11 patients - 21%) and brain metastases (15 patients - 28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months. Conclusions. While patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.
Keywords: non-small cell lung cancer, EGFR activating mutations, gemicitabine, erlotinib
Published in DiRROS: 11.04.2024; Views: 86; Downloads: 20
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5. Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer : a randomized phase II clinical trialMartina Vrankar, Matjaž Zwitter, Tanja Bavčar-Vodovnik, Ana Milič, Viljem Kovač, 2014, original scientific article Abstract: The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid. Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60-66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1-5 and 29-33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results. From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively. Conclusions. Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance
Keywords: induction chemotherapy, non-small cell lung cancer, radiation therapy, randomized clinical trial
Published in DiRROS: 11.04.2024; Views: 83; Downloads: 20
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6. The effect of heat treatment on the interface of 155 PH martensitic stainless steel and SAF 2507 duplex steel in functionally graded AM componentsMartina Koukolíková, Pavel Podaný, Sylwia Rzepa, Michal Brázda, Aleksandra Kocijan, 2023, original scientific article Abstract: Multi-material components, also known as functionally graded materials (FGMs), are innovative materials that possess unique properties due to their composition and have many potential applications in engineering and science. The effect of the heat treatment (HT) of functionally graded materials 15–5 precipitation-hardened (PH) martensitic steel and SAF 2507 duplex stainless steel (and the opposite order of deposition, i.e. SAF 2507 first followed by 15–5 PH stainless steel) on the interface microstructures was systematically investigated in the presented research. The choice of HT followed the trend of optimum post-processing for the individual alloys. A significant modification in the interface microstructure, characterized in the microstructural transition zone (MTZ) formed above the fusion line. Mechanical properties by miniaturized testing method including hardness measurement characterized both types of interfaces. The sequence of the materials’ application did not have a significant effect on their final mechanical tensile properties in the heat-treated states. Nevertheless, the microstructural change at the MTZ led to drop in the hardness at the interface. The research presents heat-treated FGMs in a horizontal configuration to form a high-quality metallurgical joint between heterogeneous materials manufactured by powder-based directed energy deposition method.
Keywords: heat treatment, additive manufacturing, martensitic stainless steel, duplex steel, microstructure, mechanical properties
Published in DiRROS: 04.04.2024; Views: 54; Downloads: 11
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7. Additive manufacturing multi-material components of SAF 2507 duplex steel and 15-5 PH martensitic stainless steelMartina Koukolíková, Pavel Podaný, Sylwia Rzepa, Michal Brázda, Aleksandra Kocijan, 2023, original scientific article Abstract: The study reports the successful deposition of 15–5 precipitation-hardened (PH) martensitic steel on SAF 2507 duplex stainless steel (and vice versa) to form functionally graded materials (FGMs) using powder-based, directed-energy-deposition (DED) technology. The evolution of the microstructure and the mechanical properties of the 15–5 PH/SAF 2507 functionally graded material in the as-built state were investigated systematically. The results proved that the microstructural transition zone (MTZ) is formed above the fusion line due to the dilution effect of both steels. The phase composition of the MTZ consists of ferrite and, in comparison to the base materials, an increased amount of austenite. The interface has the lowest hardness owing to the formation of a significant proportion of the austenitic phase. However, the tensile mechanical properties were not affected by the interface as failure occurred in both SAF 2507 and at the interface regions. The research presents a promising application of FGMs in a horizontal configuration to form a high - quality, metallurgical joint between heterogeneous materials. This study introduces a novel approach by additive manufacturing (AM) of heterogeneous multi-materials, merging the favorable properties of duplex SAF 2507 and martensitic 15-5 PH stainless steels through superior metallurgical bonding. The combination of SAF 2507 and 15-5 PH in a functionally graded material has not been previously explored, as the existing studies deal with the duplex stainless steels SAF 2507 and either martensitic stainless-steel 15-5 PH deposited separately by laser powder-bed-fusion (L-PBF) or DED methods. This research pioneers the investigation of these materials in tandem, paving the way for the development of novel FGMs with optimized properties for specific applications. The resulting FGM exhibits exceptional corrosion resistance and high strength, making it highly versatile for applications in diverse industries such as offshore oil and gas production, aerospace, aviation, and chemical processing equipment.
Keywords: directed energy deposition, functionally graded materials, miniaturized specimen testing methods, SAF 2507, 15-5 PH
Published in DiRROS: 04.04.2024; Views: 54; Downloads: 25
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8. Keep it simple : improving the ex situ culture of Cystoseira s.l. to restore macroalgal forestsAna Lokovšek, Valentina Pitacco, Domen Trkov, Leon Lojze Zamuda, Annalisa Falace, Martina Orlando-Bonaca, 2023, original scientific article Abstract: Brown algae from genus Cystoseira s.l. form dense underwater forests that represent the most productive areas in the Mediterranean Sea. Due to the combined effects of global and local stressors such as climate change, urbanization, and herbivore outbreaks, there has been a severe decline in brown algal forests in the Mediterranean Sea. Natural recovery of depleted sites is unlikely due to the low dispersal capacity of these species, and efficient techniques to restore such habitats are needed. In this context, the aims of our study were (1) to improve and simplify the current ex situ laboratory protocol for the cultivation of Gongolaria barbata by testing the feasibility of some cost-effective and time-efficient techniques on two donor sites of G. barbata and (2) to evaluate the survival and growth of young thalli during the laboratory phase and during the most critical five months after out-planting. Specifically, the following ex situ cultivation methods were tested: (A) cultivation on clay tiles in mesocosms with culture water prepared by three different procedures (a) filtered seawater with a 0.22 μm filter membrane, (b) filtered seawater with a 0.7 μm filter membrane (GF), and (c) UV-sterilized water, and (B) cultivation on clay tiles in open laboratory systems. After two weeks, all thalli were fixed to plastic lantern net baskets suspended at a depth of 2 m in the coastal sea (hybrid method), and the algal success was monitored in relation to the different donor sites and cultivation protocol. The satisfactory results of this study indicate that UV-sterilized water is suitable for the cultivation of G. barbata in mesocosm, which significantly reduces the cost of the laboratory phase. This opens the possibility of numerous and frequent algal cultures during the reproductive period of the species. Additionally, if the young thalli remain in the lantern net baskets for an extended period of several months, they can grow significantly in the marine environment without being exposed to pressure from herbivorous fish.
Keywords: gojenje ex situ, obnova habitata, izboljšanje metodologije, gozdički rjavih alg, ex situ cultivation, mesocosm, open system, method improvement, brown algal forests restoration
Published in DiRROS: 29.03.2024; Views: 94; Downloads: 47
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10. Seismogenic depth and seismic coupling estimation in the transition zone between Alps, Dinarides and Pannonian Basin for the new Slovenian seismic hazard modelPolona Zupančič, Barbara Šket Motnikar, Michele M. C. Carafa, Petra Jamšek Rupnik, Mladen Živčić, Vanja Kastelic, Gregor Rajh, Martina Čarman, Jure Atanackov, Andrej Gosar, 2024, original scientific article Abstract: Seismogenic depth and seismic coupling are important inputs into seismic hazard estimates. Although the importance of seismic coupling is often overlooked, it significantly impacts seismic hazard results. We present an estimation of upper and lower seismogenic depth and expected hypocentral depth and seismic coupling in the transition zone between the Alps, Dinarides and Pannonian Basin, characterized by a complex deformation pattern, highly variable crustal thickness, and moderate seismic hazard, supporting the development of the 2021 seismic hazard model of Slovenia. The hazard model was based on three seismic source models: area source model, fault source model and smoothed seismicity (point) source model. We estimated the lower seismogenic depth using seismological and geological data and compared them. The seismological estimate was based on two regional earthquake catalogues prepared for this study. In the area source model, estimates of lower seismogenic depth from seismological data are deeper or equal to the ones derived from geological data, except in one case. In the fault source model, we analysed each fault individually and chose seismological lower depth estimates in 12 among 89 faults as more representative. The seismogenic thickness for each individual fault source was determined for seismic coupling determination. The seismic coupling was assessed by two approaches, i.e. we chose the most trusted value from the literature, and the value determined for each fault individually by using the approach based on the updated regional fault and earthquake data sets. The final estimate of seismic coupling ranges from 0.77 to 0.38. We compared the tectonic moment rate based on long-term slip rate using different values of seismic coupling with the seismic moment rate obtained from the earthquake catalogue. The analysis is done for the whole area, as well as for the individual area zones. The analysis of N–S components of estimated slip for the largest faults in the area of west Slovenia shows that the regional geological and geodetic shortening rates are comparable. The total activity rate of three global seismic source models is compared, which gives up to a 10 % difference. Our results contribute to a better understanding of the seismic activity in the region. The presented approach for seismic coupling estimation can be applied in cases where the total slip rate is given instead of its seismic part and can be used at regional or national level. The approach is also suitable for the cross-border harmonization of the European seismic hazard modelling data.
Keywords: seismic hazard, modeling, Slovenia
Published in DiRROS: 18.03.2024; Views: 111; Downloads: 63
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