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1.
Retrospective analysis of treatment-naive Slovenian patients with metastatic melanoma treated with pembrolizumab : real-world experience
Nežka Hribernik, Marko Boc, Janja Ocvirk, Jasna Knez Arbeiter, Tanja Mesti, Marija Ignjatović, Martina Reberšek, 2020, izvirni znanstveni članek

Povzetek: Based on recent data from clinical trials, the immune checkpoint inhibitor pembrolizumab prolongs survival and has a good toxicity profile in patients with advanced or metastatic melanoma. However, the question remains whether these results are transmitted into daily clinical practice. The aim of this study was to assess the efficacy and toxicity of pembrolizumab in treatment-naive patients with metastatic melanoma in everyday clinical practice in Slovenia and compare it to the results from clinical trials. Patients and methods. This observational retrospective cohort study included 138 consecutive metastatic treatment-naive melanoma patients treated with pembrolizumab at the Institute of Oncology Ljubljana in Slovenia, from January 2016 to December 2018. Patient and treatment characteristics were retrospectively collected from hospital data base. Statistical data was obtained using the SPSS software version 22. Survival rate was calculated with the Kaplan-Meier method. Observation period took place between January 2016 and the end of June 2019. Results. The estimated median overall survival (OS) was 25.1 months (95% CI, 14.6%35.6) and the median progressionfree survival (PFS) was 10.7 months (95% CI, 5.9%15.4). Among all patients, 29 (21.0%) achieved complete response, 31 (22.5%) partial response and 23 (16.7%) reached stable disease. The number of organs with metastatic involvement and the level of baseline lactate dehydrogenase (LDH) concentration had significant influence on survival rates. Immune-related adverse events (irAE) were reported in 88 (63%) patients, while grade 3%4 irAE occurred in 12 (8.7%). Due to toxicity, 16 (11.6%) patients discontinued the treatment. Conclusions. Our real-world data from single centre retrospective analysis of treatment-naive metastatic melanoma patients treated with pembrolizumab showed inferior median OS and similar median PFS, compared to the results from clinical trials. However, patients with normal serum levels of LDH and a small number of organs with metastatic involvement had comparable survival outcomes. Toxicity rates of pembrolizumab were quite similar. These results further support the use of pembrolizumab for metastatic treatment-naive melanoma patients.
Ključne besede: immunotherapy, pembrolizumab, metastatic melanoma, treatment-naive
Objavljeno v DiRROS: 11.07.2024; Ogledov: 16; Prenosov: 2
.pdf Celotno besedilo (696,58 KB)

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Phytoplankton assemblage over a 14-year period in the Adriatic Sea : patterns and trends
Sanda Skejić, Blanka Milić Roje, Frano Matić, Jasna Arapov, Janja Francé, Mia Bužančić, Ana Bakrač, Maja Straka, Živana Ninčević Gladan, 2024, izvirni znanstveni članek

Povzetek: Considering the role of phytoplankton in the functioning and health of marine systems, it is important to characterize its responses to a changing environment. The central Adriatic Sea, as a generally oligotrophic area, is a suitable environment to distinguish between regular fluctuations in phytoplankton and those caused by anthropogenic or climatic influences. This study provides a long-term perspective of phytoplankton assemblage in the central eastern Adriatic Sea, with 14 years of continuous time series data collected at two coastal and two offshore stations. The predominant phytoplankton groups were diatoms and phytoflagellates, but their proportion varied depending on the vicinity of the coast, as evidenced also by the distribution of chlorophyll a. In the coastal environment, the phytoplankton biomass was substantially higher, with a higher proportion of microphytoplankton, while small phytoplankton accounted for the majority of biomass in the offshore area. In addition, a decreasing trend in diatom abundance was observed in the coastal waters, while such trend was not so evident in the offshore area. Using a neural gas algorithm, five clusters were defined based on the contribution of the major groups. The observed increase in diversity, especially in dinoflagellates, which outnumber diatom taxa, could be a possible adaptation of dinoflagellates to the increased natural solar radiation in summer and the increased sea surface temperature.
Ključne besede: phytoplankton community, long-term data, diversity, chlorophyll a, neural gas analysis, solar radiation, Adriatic Sea
Objavljeno v DiRROS: 11.07.2024; Ogledov: 13; Prenosov: 5
.pdf Celotno besedilo (2,46 MB)
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Induction chemotherapy, chemoradiotherapy and consolidation chemotherapy in preoperative treatment of rectal cancer : long-term results of phase II OIGIT-01 Trial
Danijela Golo, Jasna But-Hadžić, Franc Anderluh, Erik Brecelj, Ibrahim Edhemović, Ana Jeromen, Mirko Omejc, Irena Oblak, Ajra Šečerov Ermenc, Vaneja Velenik, 2018, izvirni znanstveni članek

Povzetek: The purpose of the study was to improve treatment efficacy for locally advanced rectal cancer (LARC) by shifting half of adjuvant chemotherapy preoperatively to one induction and two consolidation cycles. Patients and methods Between October 2011 and April 2013, 66 patients with LARC were treated with one induction chemotherapy cycle followed by chemoradiotherapy (CRT), two consolidation cycles, surgery and three adjuvant capecitabine cycles. Radiation doses were 50.4 Gy for T2-3 and 54 Gy for T4 tumours in 1.8 Gy daily fraction. The doses of concomitant and neo/adjuvant capecitabine were 825 mg/m2/12h and 1250mg/m2/12h, respectively. The primary endpoint was pathologic complete response (pCR). Results Forty-three (65.1%) patients were treated according to protocol. The compliance rates for induction, consolidation, and adjuvant chemotherapy were 98.5%, 93.8% and 87.3%, respectively. CRT was completed by 65/66 patients, with G % 3 non-hematologic toxicity at 13.6%. The rate of pCR (17.5%) was not increased, but N and the total-down staging rates were 77.7% and 79.3%, respectively. In a median follow-up of 55 months, we recorded one local relapse (LR) (1.6%). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 64.0% (95% CI 63.89%64.11) and 69.5% (95% CI 69.39%69.61), respectively. Conclusions In LARC preoperative treatment intensification with capecitabine before and after radiotherapy is well tolerated, with a high compliance rate and acceptable toxicity. Though it does not improve the local effect, it achieves a high LR rate, DFS, and OS.
Ključne besede: rectal cancer, neoadjuvant chemotherapy, preoperative chemoradiotherapy
Objavljeno v DiRROS: 11.06.2024; Ogledov: 74; Prenosov: 49
.pdf Celotno besedilo (1,27 MB)
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Implant-prosthetic rehabilitation after radiation treatment in head and neck cancer patients : a case-series report of outcome
Jasna Cotič, Jure Jamšek, Milan Kuhar, Nataša Ihan Hren, Andrej Kansky, Mutlu Özcan, Peter Jevnikar, 2017, izvirni znanstveni članek

Povzetek: Background. Slovenia has a high burden of head and neck cancer. Patients are mostly treated with surgery followed by radiation therapy. Advanced surgical and prosthodontic techniques have expanded the rehabilitation options. The aim of the study was to review the outcome of implant-prosthetic treatment after radiation therapy. Patients and methods. Twenty irradiated head and neck cancer patients who received a removable implantsupported denture at the University Medical Centre Ljubljana were included in the study. Kaplan-Meier survival analysis, Cox proportional hazard models and logistic regression were used to assess the implant survival and success rate. Results. Twenty patients had 100 implants inserted. The estimated implant survival rate was 96% after 1 year and 87% after 5 years. Failures were mostly observed before loading (91.2%). Implants inserted in the transplanted bone were significantly more likely to fail. Out of 89 implants supporting the dentures, 79 implants (88.7%) were successful, meaning that they were functionally loaded and exhibited no pain, radiolucency or progressive bone loss. Prosthetic treatment was significantly less successful in older patients. The attachment system and the number of implants did not have a statistically significant influence on the success rate. Conclusions. Implant-supported dentures have been shown to be a reliable treatment modality after head and neck cancer surgery and radiation therapy. Possible early failures should be communicated with the patients.
Ključne besede: head and neck cancer, radiation therapy, dental implants
Objavljeno v DiRROS: 03.06.2024; Ogledov: 128; Prenosov: 56
.pdf Celotno besedilo (586,82 KB)

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Health-related quality of life assessed by the EORTC QLQ-C30 questionnaire in the general Slovenian population
Vaneja Velenik, Ajra Šečerov Ermenc, Jasna But-Hadžić, Vesna Zadnik, 2017, izvirni znanstveni članek

Povzetek: 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.
Objavljeno v DiRROS: 24.05.2024; Ogledov: 207; Prenosov: 142
.pdf Celotno besedilo (570,58 KB)

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The impact of anaemia on treatment outcome in patients with squamous cell carcinoma of anal canal and anal margin
Irena Oblak, Monika Češnjevar, Mitja Anžič, Jasna But-Hadžić, Ajra Šečerov Ermenc, Franc Anderluh, Vaneja Velenik, Ana Jeromen, Peter Korošec, 2016, izvirni znanstveni članek

Povzetek: Radiochemotherapy is the main treatment for patients with squamous cell carcinoma of the anal canal. Anaemia is reported to have adverse effect on survival in cancer patients. The aim of the study was to evaluate the influence of anaemia on radiochemotherapy treatment outcome in patients with squamous cell carcinoma of the anal canal. Patients and methods. One hundred consecutive patients with histologically confirmed squamous cell carcinoma of the anal canal were treated radically with 3-dimensional conformal or intensity-modulated radiation therapy followed by brachytherapy or external beam radiotherapy boost and with concurrent mitomycin C and 5-fluorouracil. The influence on survival of pre-treatment, mean on-treatment and end-of-treatment haemoglobin (Hb) concentrations was studied. Results. The 5-year locoregional control, disease free survival, disease specific survival and overall survival rates for all patients were 72%, 71%, 77% and 62%, respectively. In univariate analysis, patients with pre-treatment and end-oftreatment Hb > 120 g/L survived statistically significantly better compared to patients with Hb % 120 g/L. Patients with mean on-treatment Hb > 120 g/L only had statistically significant better locoregional control and overall survival than patients with Hb % 120 g/L. In multivariate analysis, independent prognostic factors were pre-treatment Hb (> 120 g/L vs. % 120 g/L) for overall survival (hazard ratio [HR] = 0.419, 95% confidence interval [CI] = 0.190%0.927, p = 0.032) and stage (I & II vs. III) for disease specific (HR = 3.523, 95% CI = 1.375%9.026, p = 0.009) and overall survival (HR = 2.230, 95% CI = 1.167%4.264, p = 0.015). Conclusions. The pre-treatment, mean on-treatment and end-of-treatment Hb concentration > 120 g/L carried better prognosis for patients for with squamous cell carcinoma of the anal canal treated with radiochemotherapy. The pre-treatment Hb > 120 g/L was an independent prognostic factor for overall survival of patients with anal canal cancer.
Ključne besede: anaemia, anal canal squamous cell carcinoma, radiochemotherapy
Objavljeno v DiRROS: 30.04.2024; Ogledov: 227; Prenosov: 127
.pdf Celotno besedilo (488,29 KB)
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Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer
Ivica Ratoša, Irena Oblak, Franc Anderluh, Vaneja Velenik, Jasna But-Hadžić, Ajra Šečerov Ermenc, Ana Jeromen, 2015, izvirni znanstveni članek

Povzetek: To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution. Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4-6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival. Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five patients (5.6% of all treated patients or 8.8% of all operated patients). Down-staging was recorded in 49 patients (86%), in one patient (1.8%) the stage after radiochemotherapy was unchanged while in seven patients (12.3%) the pathological stage was higher than clinical, mainly due to higher pN stage. No death was recorded during preoperative radiochemotherapy. Most grade 3 and 4 toxicities were due to vomiting, nausea and bone marrow suppression (granulocytopenia). Twentysix (45.6%) patients died due to GEJ or gastric carcinoma, one died because of septic shock following the surgery and a reason for two deaths was unknown. Twenty-eight patients (49.1%) were disease free at the time of analysis, while 29 patients (50.9%) developed the recurrence, mostly as distant metastases. At two years, locoregional control, diseasefree survival, disease-specific survival and overall survival were 82.9%, 43.9%, 56.9% and 53.9%, respectively. Preoperative radiochemotherapy was feasible in our group of patients and had acceptable toxicity. Majority of patients achieved down-staging, allowing greater proportion of radical resections (R0), which are essential for patientsʼ cure.
Ključne besede: neoadjuvant radiochemotherapy, perioperative chemotherapy, chemotherapy, adenocarcinoma, carcinoma, surgery
Objavljeno v DiRROS: 23.04.2024; Ogledov: 192; Prenosov: 64
.pdf Celotno besedilo (1,18 MB)

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Capecitabine in adjuvant radiochemotherapy for gastric adenocarcinoma
Irena Oblak, Marija Skoblar Vidmar, Franc Anderluh, Vaneja Velenik, Ana Jeromen, Jasna But-Hadžić, 2014, izvirni znanstveni članek

Povzetek: Background. In patients with non-metastatic gastric cancer surgery still remains the treatment of choice. Postoperative radiochemotherapy with 5-fluorouracil and leucovorin significantly improves the treatment outcome. The oral fluoropyrimidines, such as capecitabine, mimic continuous 5-fluorouracil infusion, are at least as effective as 5-fluorouracil, and such treatment is more comfortable for the patients. Patients and methods. In the period from October 2006 to December 2009, 101 patients with gastric cancer in stages Ib-IIIc were treated with postoperative chemoradiation with capecitabine. Distal subtotal resection of the stomach was performed in 46.3%, total resection in 50.5% and multivisceral resection in 3.2% of patients. The main endpoints of this study were loco-regional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). The rates of acute side-effects were also estimated. Results. Seventy-seven percent of patients completed the treatment according to the protocol. The median followup time of all patients was 3.9 years (range: 0.4-6.3 years) and in survivors it was 4.7 years (range: 3.2-6.3 years). No death occurred due to the therapy. Acute toxicity, such as nausea and vomiting, stomatitis, diarrhoea, hand-foot syndrome and infections of grade 3 or 4, occurred in 5%, 1%, 2%, 8.9% and 18.8% of patients, respectively. On the close-out date 63.4% patients were still alive and with no signs of the disease. The 4-years follow-up survey showed that LRC, DFS, DSS and OS were 95.5%, 69.2%, 70.7%, and 66.2%, respectively. Higher pN-stage and splenectomy were found to be independent prognostic factors for all four types of survival and perineural invasion and lower treatment intensity for DFS, DSS and OS.
Ključne besede: gastric cancer, adjuvant therapy, radiochemotherapy
Objavljeno v DiRROS: 11.04.2024; Ogledov: 224; Prenosov: 64
.pdf Celotno besedilo (519,56 KB)

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