11. Cetuximab in preoperative treatment of rectal cancer - term outcome of the XERT trialVaneja Velenik, Janja Ocvirk, Irena Oblak, Franc Anderluh, 2012, original scientific article Abstract: Preoperative capecitabine-based chemoradiotherapy (CRT) is feasible for the treatment of resectable locally advanced rectal cancer (LARC). To try to improve efficacy, we conducted a phase II studz in which the epidermal growth factor receptor-targeting monoclonal antibody cetuximab was added to capecitabine-based CRT. The results for long-term survival and for an analysis investigating the relationship between survival and patient and disease characteristics, including tumour KRAS mutation status, and surgery type, are presented. Patients with resectable LARC received capecitabine (1250mg/m2 twice daily, orally) for 2 weeks followed by cetuximab alone (400 mg/m2 for 1 week) and then with CRT (250 mg/m2/week) comprising capecitabine (825 mg/m2 twice daily) and radiotherapy to the small pelvis (45 Gz in 25 1.8-Gz fractions), five dazs a week for five weeks. Surgery was conducted six weeks following CRT, with post-operative chemotherapy with capecitabine (1250 mg/m2 twice daily for 14 days every 21 days) three weeks later. Forty-seven patients were enrolled and 37 underwent treatment. Twenty-eight of the patients (75.7%) had T3N+ disease. Thirty-six patients were evaluable for efficacy. The median follow-up time was 39.0 months (range 5.0-87.0). The three-year local control, disease-free survival, relapse-free survival and overall survival rates were 96.9% (95% CI 90.0-100), 72.2% (57.5-86.9), 74.3% (95% CI 59.8-88.8) and 68.1% (95% CI 36.7-99.4), respectively. There was no significant association between survival and gender, age, tumour location in the rectum, type of surgery, pathological T or N status, tumour regression grade or tumour KRAS mutation status, although sample sizes were small. Preoperative cetuximab plus capecitabine-based CRT was feasible in patients with resectable LARC and was associated with an impressive three-year local control rate. The use of tumour KRAS mutation status as a biomarker for the efficacy of cetuximab-based regimens in this setting requires further investigation.
Published in DiRROS: 21.03.2024; Views: 72; Downloads: 27
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12. Long term outcome after combined modality treatment for anal cancerIrena Oblak, Primož Petrič, Franc Anderluh, Vaneja Velenik, Albert-Peter Fras, 2012, original scientific article Abstract: Background. The aim of the retrospective study was to evaluate the effectiveness and toxicity of radiochemotherapy in patients with squamous cellcarcinoma of the anal canal treated at a single institution. Patients and methods. Between 1/2003 and 9/2010, 84 patients were treated with radical radiochemotherapy at the Institute of Oncology Ljubljana, Slovenia. The treatment consisted of 3-dimensional conformal external beam radiotherapy with concurrent chemotherapy (5-fluorouracil and mytomycin C), followed by brachytherapy or external beam boost. The toxicity of therapy and its effectiveness were assessed. Results. The treatment was completed according tothe protocol in 79.8% of patients. The median follow-up time of 55 survivors was 53 months (range: 16-105 months). The 5-year locoregional control(LRC), disease-free survival (DFS), disease-specific survival (DSS), overall survival (OS) and colostomy-free survival (CFS) rates were 71%, 68%, 81%, 67% and 85%, respectively. No treatment-related mortality was observed. The most frequent acute side-effect of the treatment was radiodermatitis (grade 3-4 in 58.2% of patients). LENT-SOMA grade 3-4 late radiation side effects were observed in 15 (18%) patients. In patients with brachytherapy boost a trend of less late side effects was observed compared to patients with external beam boost (P=0.066). On multivariate analysis, complete clinicaldisease response was identified as an independent prognostic factor for LRC, DFS and DSS, the salvage surgery for LRC and DFS, whereas Hb below 120 g/l retained its independent prognostic value for OS. Conclusions. Radiochemotherapy provides an excellent disease control and the survival with preserving anal sphincter function in majority of patients. Surgical salvage with abdominoperineal resection for persistent or recurrent disease has curative potential.
Published in DiRROS: 21.03.2024; Views: 74; Downloads: 30
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13. CD133/prominin1 is prognostic for GBM patient's survival, but inversely correlated with cysteine cathepsine' expression in gliobastoma derived spheroidsSeyed Yousef Ardebili, Irena Zajc, Boris Gole, Benito Campos, Christel Herold-Mende, Sara Drmota Prebil, Tamara Lah Turnšek, 2011, original scientific article Abstract: Introduction. CD133 is a marker for a population of glioblastoma (GBM) and normal neural stem cells (NNSC). We aimed to reveal whether the migratory potential and differentiation of these stem cells is associated with CD133 expression and with cathepsin proteases (Cats). Materials and methods. The invasiveness of normal NNSC, GBM/CD133+ cell lines and GBM spheroids was evaluated in 3D collagen, as well as of U87-MG and normal astrocytes (NHA) grown in monolayers in 2D Matrigel. Expression of Cats B, L and S was measuredat mRNA and activity levels and their relation to invasiveness, to CD133 mRNA in 26 gliomas, and to the survival of these patients. Results. The average yield of CD133+ cells from GBM samples was 9.6%. Survival of patients with higher CD133 mRNA expression was significantly shorter (p< 0.005). Invasion, associated with proteolytic degradation of matrix, was higher in normal stem cells and GBM spheroids and cells than in isolated GBM CD133+ cells. In glioma samples, there was no correlation between CD133 mRNA expression and Cat mRNAs, but there was an inverse correlation with Cat activities. Conclusions. The study confirms CD133 as a prognostic marker for the survival of GBM patients. We demonstrated that NNSC have higher invasion potential and invade the collagen matrix in a mode different from that of GBM,initiating stem cell spheres. This result could have implications for the design of new therapeutics, including protease inhibitors that specifically target invasive tumour stem cells. Increased activity of cathepsins in CD133- cells suggests their role in the invasive behaviour of GBM.
Published in DiRROS: 19.03.2024; Views: 109; Downloads: 27
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18. Postoperative radiochemotherapy for gastric adenocarcinoma : long term resultsIrena Oblak, Franc Anderluh, Vaneja Velenik, 2009, original scientific article Abstract: Background. To analyze the efficacy of postoperative radiochemotherapy with 5-florouracil (5-FU) and leucovorin (LV) applied in the patients with gastric carcinoma treated in a single institution. Patients and methods. Between 2001 and 2004, 123 patients with resected gastric adenocarcinoma were treated with postoperative concomitant radiochemotherapy with 5-FU and LV. The adjuvant treatment consisted of five cycles of chemotherapy with 5-FU (425mg/m2 IV) andLV (20 mg/m2 IV) and concomitant radiotherapy with the total dose of 45 Gy.Results. The treatment was completed according to the protocol in 82% of patients. The frequency and severity of early toxic effects induced by radiochemotherapy were manageable. Median follow-up time of 56 survivors was 64.5 months (range: 51.7-96.4 months). The 5-year locoregional control (LRC), diseasefree survival (DFS), disease-specific survival (DSS) and overall survival (OS) were 81%, 48.3%, 50.4%, and 48.4%, respectively. The multivariate analysis showed that the tumor involvement of cardia and low intensity of chemotherapy were independent adverse prognostic factors for DSS and OS. More advanced pT-stage and tumors with diffuse growth type according to Lauren were identified as negative independent prognostic factor for OS. They were also on the threshold of statistical significance for DSS. Conclusions. Postoperative radiochemotherapy for gastric carcinoma has acceptable toxicity, and is effective particularly in regard to LRC. High incidence of distant metastases calls for more effective systemic regimens.
Published in DiRROS: 08.03.2024; Views: 85; Downloads: 26
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19. Relevance of cold-rolling technology for the texture and anisotropy of EN AW-8011A aluminum alloysJakob Kraner, Kyung Il Kim, Bonghwan Kim, Shae K. Kim, Irena Paulin, 2023, original scientific article Keywords: aluminium alloys, cold rolling, SEM-EBSD, textures, anisotropy
Published in DiRROS: 08.03.2024; Views: 95; Downloads: 44
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