Onkologija : Slovenian Journal of Oncology
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An overview of recommendations for genetic and preventive management of patients with Li-Fraumeni syndrome
Germline pathogenic variants in the TP53 gene are associated with an increased risk of developing cancer. The most penetrant of these variants are associated with Li-Fraumeni syndrome (LFS), a rare hereditary cancer predisposition syndrome. In this overview, we aim to present the genetic causes and clinical characteristics of the syndrome, as well as recommendations for genetic testing and preventive surveillance in individuals with LFS. This predisposition has been linked to a wide variety of tumours, which occur in all age groups, the most common being adrenocortical carcinoma, breast cancer, central nervous system tumours, osteosarcoma, and soft tissue sarcoma. The protein product of the TP53 gene is involved in many cellular processes, including the repair of replication errors accumulated during cell division and programmed cell death. Our understanding of the syndrome and management of individuals with LFS has progressed greatly since it was first described. In parallel, indications and methods for performing genetic testing have also evolved over the years. Preventive surveillance after diagnosis of LFS is very intensive and includes yearly whole-body magnetic resonance imaging. Its aim is to enable better treatment through early detection of malignant tumours, which leads to improved survival and quality of life for individuals with LFS. The majority of patients with LFS seen at the Institute of Oncology Ljubljana in the years 2015–2026 opted for surveillance in accordance with the guidelines and managed to adhere to their preventive programmes.
Copyright (c) 2026 Maša Smrdel, Mateja Krajc, Ana Blatnik https://creativecommons.org/licenses/by/4.0
Comparative analysis of two radiotherapy approaches within total neoadjuvant therapy for high-risk locally advanced rectal cancer
Background: Total neoadjuvant therapy (TNT) has become a standard of care for patients with locally advanced rectal cancer (LARC) who present with high risk features on magnetic resonance imaging (MRI). Despite its increasing adoption, the optimal sequencing of individual treatment components and the long term outcomes of a non operative watch and wait (W&W) strategy after TNT remain insufficiently defined. Moreover, the impact of radiotherapy technique on treatment effectiveness, local disease control, and long term outcomes in routine clinical practice has not been clearly established. Patients and Methods: This comparative analysis included two consecutive cohorts of patients with LARC and at least one MRI defined high risk feature, treated at the Institute of Oncology Ljubljana with an institutional “sandwich” TNT protocol. The study population comprised 240 patients: 35 treated with three dimensional conformal radiotherapy (3D CRT cohort) and 205 treated with intensity modulated radiotherapy/volumetric modulated arc therapy with a simultaneous integrated boost (IMRT/VMAT SIB cohort). The primary endpoint was overall complete response, defined as pathological complete response (pCR) or clinical complete response (cCR) with inclusion in a structured W&W follow up strategy. Secondary endpoints were pCR, major pathological response (MPR), R0 resection rate, downstaging, local recurrence, disease free survival (DFS) and overall survival (OS). For the primary and key secondary outcomes, we performed unadjusted formal comparisons of proportions as well as exploratory adjusted analyses using Firth logistic regression; for OS up to 36 months, we additionally performed a weighted Cox model. Results: The study population consisted of 240 patients, 35 in the 3D CRT cohort and 205 in the IMRT/VMAT SIB cohort. Overall complete response was achieved in 14,3% of patients in the 3D CRT cohort and in 29,5% of patients in the IMRT/VMAT SIB cohort. The pCR rates were 9,4% in the 3D CRT cohort and 19,3% in the IMRT/VMAT SIB cohort, while MPR rates were 30,8% and 37,6%, respectively. R0 resection was achieved in all operated patients in the 3D CRT cohort and in 94,5% of operated patients in the IMRT/VMAT SIB cohort. In the Firth model, IMRT/ VMAT-SIB showed a trend toward a higher overall complete response (OR 2,39; 95% CI 0,95–7,08; p = 0.064), whereas no statistically significant effect was confirmed for pCR (OR 2,20; 95% CI 0,73–8,75; p = 0.171). Conclusions: Both radiotherapy techniques allow feasible and oncologically effective delivery of the institutional “sandwich” TNT protocol in patients with MRI defined high risk LARC. In our single-institution experience, numerically more favourable local response outcomes were observed in the IMRT/VMAT-SIB cohort than in the 3D-CRT cohort, but formal comparisons did not confirm these differences statistically. Given the retrospective design, partially overlapping historical cohorts, and limited number of events, no definitive conclusions regarding the superiority of either technique can be drawn.
Copyright (c) 2026 Manuel Ramanović https://creativecommons.org/licenses/by/4.0
Implantable intrathecal pumps for refractory cancer pain
Cancer pain is often inadequately managed with standard systemic therapies. Targeted intrathecal administration of analgesics via implantable (internal) intrathecal pumps may improve analgesia and reduce systemic adverse effects. However, treatment with external pumps may place a substantial burden on patients and their caregivers due to the frequent need for medication reservoir refills. In addition, external pumps can be cumbersome and may interfere with patients’ daily activities. Recently, implantable intrathecal pumps placed in the subcutaneous tissue have become increasingly used. These devices allow the administration of highly concentrated drug solutions and less frequent refilling, which may significantly improve quality of life. We conducted a prospective pilot study including eight patients with advanced cancer and refractory pain. Two patients received analgesic therapy via an implantable intrathecal pump, while six were treated using a subcutaneous pump. Pain intensity and quality of life were assessed using the Visual Analogue Scale (VAS), the Edmonton Symptom Assessment System (ESAS), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Assessments were performed during the first four weeks after pump implantation. Intrathecal pump therapy was associated with a faster and more sustained reduction in pain compared with subcutaneous pumps. Patients treated with intrathecal pumps demonstrated better overall health status, more favourable functional and symptom profiles, and a lower incidence of treatment-related adverse effects. Implantable intrathecal pumps may enable more effective pain control and significantly improve quality of life in carefully selected patients with refractory cancer pain compared with subcutaneous administration. Larger, well-designed prospective studies are needed to confirm these findings.
Copyright (c) 2026 Teodora Zupanc https://creativecommons.org/licenses/by/4.0
Impact of mean heart dose on mortality after high-dose radiotherapy for lung cancer
Background: Cardiovascular complications represent an important late adverse effect of thoracic radiotherapy in patients with lung cancer. Mean heart dose (MHD) is a commonly used dosimetric parameter in radiotherapy planning; however, the optimal threshold associated with patient survival has not yet been clearly defined. The aim of this study was to evaluate the impact of MHD on overall survival following high-dose radiotherapy for lung cancer. Methods: We retrospectively analysed patients with lung cancer treated with thoracic radiotherapy at the Institute of Oncology Ljubljana between 2018 and 2022. Clinical characteristics, treatment data, and dosimetric parameters from radiotherapy plans were analysed. Mean heart dose was evaluated in 5-Gy increments. Overall survival was estimated using the Kaplan-Meier method, and the impact of individual variables was assessed using Cox regression analysis. Results: A total of 460 patients were included in the analysis. The mean age was 66 years, and the majority of patients had locally advanced disease (stage III). With a median follow-up of 28.5 months, the median overall survival was 28.3 months (95% CI 25.2- 31.6). The mean heart dose was 9.09 Gy (range 0.05-34.79 Gy). When comparing groups according to the MHD threshold of 20 Gy, patients with MHD < 20 Gy had longer survival (31.1 months; 95% CI 26.7-35.4) compared with patients with MHD ≥ 20 Gy (23.5 months; 95% CI 16.2-30.8; p = 0.020). In multivariable analysis, MHD ≥ 20 Gy was independently associated with worse overall survival (HR 1.54; 95% CI 1.12-2.11; p = 0.008). Age ≥ 65 years (HR 1.66; p < 0.001) and poorer performance status (HR 2.02; p < 0.001) were also significant prognostic factors. Conclusion: Mean heart dose represents an important prognostic factor in lung cancer radiotherapy. Our results show that MHD < 20 Gy is associated with improved overall survival, supporting the use of this constraint in high-dose radiotherapy planning for lung cancer. Further analyses of radiation dose to individual cardiac substructures may help identify critical cardiac regions and improve individualized radiotherapy planning.
Copyright (c) 2026 Katja Šketa https://creativecommons.org/licenses/by/4.0
Clinical recommendations for the management of radiodermatitis and radiomucositis
Radiotherapy is an important part of modern cancer treatment, but it often causes side effects on the skin and mucous membranes, the most common of which are radiodermatitis and radiomucositis. The purpose of these professional recommendations is to standardize patient care, improve the recognition of early changes, and provide guidelines for the prevention, assessment, and treatment of these complications. The document addresses the etiology, risk factors, clinical presentation, and stages of radiodermatitis and radiomucositis based on the area of radiation. Special emphasis is placed on preventive measures, nursing care, nutritional support, pain management, and a multidisciplinary approach to patient care during and after radiotherapy. The recommendations are intended for healthcare professionals and staff at all levels of healthcare who are involved in the daily care of cancer patients.
Copyright (c) 2026 Sandra Gole https://creativecommons.org/licenses/by/4.0
Recommendations for the management and treatment of patients with soft tissue sarcoma emphasize the importance of individualized treatment in a referral center with a multidisciplinary sarcoma team. The only referral sarcoma center in Slovenia is the Institute of Oncology Ljubljana. Key components include imaging diagnostics using MRI and CT scans and a core needle biopsy. Surgical treatment remains the cornerstone of therapy, while radiotherapy reduces the risk of local recurrence. Systemic treatment with chemotherapy or targeted drugs is primarily considered for advanced, metastatic disease. The 2026 recommendations are available at the Institute of Oncology Ljubljana website.
Copyright (c) 2026 Marko Novak https://creativecommons.org/licenses/by/4.0
Transcriptomic stratification of advanced primary endometrial tumors by mismatch repair status
Background: Endometrial cancer (EC) is one of the most common gynaecological malignancies in developed countries and has a poor prognosis in advanced disease. The introduction of adjuvant treatment with immunotherapy has significantly improved survival in patients with advanced EC with deficient mismatch repair (MMRd), which is characterized by high microsatellite instability (MSI-H). However, more than two‑thirds of patients develop tumours with proficient mismatch repair (MMRp), which are microsatellite stable (MSS) and respond poorly to immunotherapy. This highlights a substantial clinical need for the development of new therapeutic approaches for patients with advanced EC who are MMRp-MSS. Methods: Clinical and transcriptomic data from the TCGA-UCEC cohort were downloaded using the TCGABiolinks package in RStudio. Patients with primary, advanced-stage EC and available clinical, molecular, and transcriptomic data were included. Differential gene expression according to MMR status was performed using DESeq2. Cox proportional hazards models were fitted to evaluate associations between levels of differentially expressed genes and disease-specific survival (DSS) in the MMRp-MSS subgroup. In the primary analysis, we compared MMRp-MSS tumours with MMRd-MSI-H tumours. In this analysis, MSS tumours belonging to the POLEmut, TP53alt, and nonspecific molecular profile (NSMP) subtypes were classified as MMRp-MSS. In the subanalysis, we repeated the comparison after excluding POLEmut tumours from the MMRp-MSS group (MMRp-MSS excluding POLEmut vs. MMRd-MSI-H). Results: Of the 545 patients with EC, 139 had advanced disease (27 with MMRd-MSI-H tumours and 112 with MMRp-MSS tumours). There were no significant differences in survival between the MMRp-MSS and MMRd-MSI-H subgroups. Differential gene expression analysis (|fold change| > 2, adjusted p < 0.01) identified 974 genes. Of these, 268 genes were significantly associated with DSS within the MMRp-MSS tumour group. Higher expression of genes involved in immune system activation and inhibition of the Wnt signalling pathway was associated with longer survival. In contrast, higher expression of genes involved in oncogenic signalling, immune evasion, neuronal differentiation, and extracellular matrix remodelling predicted poorer outcomes. The subanalysis comparing MMRp-MSS (excluding POLEmut) with MMRd-MSI-H showed fully comparable results: again, no survival differences were observed between the groups, and similar patterns of differential gene expression and the same functional survival‑related hubs emerged as in the primary comparison of MMRp-MSS versus MMRd-MSI-H. Conclusions: Advanced MMRp-MSS ECs are transcriptionally distinct from advanced MMRd-MSI-H tumours. Within MMRp-MSS tumours, we identified gene expression programs associated with prognosis. These findings highlight potential therapeutic targets for this high-risk subgroup and support the development of molecular subtype-adjusted treatment strategies.
Copyright (c) 2026 Marija Gjorgoska https://creativecommons.org/licenses/by/4.0
Radiotherapy intensity in patients with advanced solid cancer at the end-of-life
Introduction: Advances in oncology have raised questions about the appropriateness of treatment at the end of life. Palliative radiotherapy is not currently considered an indicator of aggressive end-of-life care. This study aimed to evaluate the use of specific oncological treatments in patients with advanced solid cancer at the end of life. Methods: We conducted a retrospective analysis of adult patients with advanced solid cancer treated exclusively at the Institute of Oncology Ljubljana who died between 2015 and 2019. We assessed the prevalence of aggressive oncological treatments in the last month and the last two weeks of life. Results: A total of 1,736 patients were included. At least one form of aggressive treatment was administered to 538 patients (31%) in the last month of life and to 250 patients (14.4%) in the last two weeks. Systemic therapy was the most common modality (15.7% in the last month; 7.2% in the last two weeks), with chemotherapy administered to 10.5% of patients in the last month and 4.4% in the last two weeks. Radiotherapy was used in 15.6% of patients in the last month and 6.8% in the last two weeks. Its use in the last month declined (2015 – 16.7% and 2019 – 12.5%), while remaining stable in the last two weeks (2015 – 6.3 % and 2019 – 6.7 %). Conclusions: Radiotherapy use in the last month of life is declining, while remaining stable in the last two weeks; however, it is still frequently used. Given its comparable use to systemic therapy, radiotherapy should be considered an indicator of aggressive care at the end of life.
Copyright (c) 2026 Nena Golob https://creativecommons.org/licenses/by/4.0
Successful genetic testing of a 59-year-old tissue sample
We present a successful genetic analysis of a 59-year-old archival formalin-fixed, paraffin-embedded (FFPE) tissue sample for the assessment of hereditary cancer predisposition. In families with a strong history of cancer where key affected relatives are deceased, standard germline testing in living family members may prove uninformative. Archival tumor material may therefore represent an important source of genetic information. In the case presented here, DNA was extracted from a tumor sample collected in 1960 and analyzed using next-generation sequencing (NGS). Despite the advanced age of the specimen, all quality criteria required for reliable molecular genetic analysis were met. A pathogenic variant, CHEK2:c.1100del p.(Thr367Metfs*15), associated with an increased risk of breast cancer, was identified. Subsequent cascade testing enabled a more accurate assessment of cancer risk among living relatives and appropriate preventive recommendations. This case demonstrates the clinical utility of archival FFPE tissue samples in the genetic evaluation of families with suspected hereditary cancer predisposition. It also highlights the importance of long-term preservation of representative histological material for diagnostic, preventive, and research purposes.
Copyright (c) 2026 Ana Blatnik, Vita Šetrajčič Dragoš, Vida Stegel, Olga Blatnik, Mateja Krajc https://creativecommons.org/licenses/by/4.0
Survival rates among Slovenian cancer patients have steadily improved over recent decades, reflecting significant advances in Slovenian oncology and the national healthcare system. The National Cancer Control Programme provides an integrated framework encompassing primary and secondary prevention, diagnostics, treatment, rehabilitation, and palliative care. To reduce the overall cancer burden, improve patients’ quality of life, and ensure economic sustainability, the consistent implementation of evidence-based preventive programmes and the provision of timely, professionally grounded treatment are essential. Over the past two decades, advances in medical science have introduced important new insights, including the integration of complementary, evidence-based methods, which have gained increasing recognition. In this context, Traditional Chinese Medicine (TCM), particularly acupuncture, has assumed a meaningful role as a supportive modality in oncology. At the Institute of Oncology Ljubljana (OIL), acupuncture has been practiced for over 40 years, primarily to alleviate treatment-related side effects and as part of multimodal pain management. In recent years, its role has further expanded within the framework of structured oncological rehabilitation (OREH).
Copyright (c) 2026 Iztok Potočnik, Vlasta Orlić Karbić https://creativecommons.org/licenses/by/4.0
Selected chapters on medical emergencies
Copyright (c) 2025 Iztok Potočnik, Helena Lenasi, Martin Erak https://creativecommons.org/licenses/by/4.0
20th Anniversary of the Department of Experimental Oncology at the Institute of Oncology Ljubljana
The twentieth anniversary of the Department of Experimental Oncology marks an important milestone in the history of research activities at the Institute of Oncology Ljubljana. Research activity at the Institute of Oncology Ljubljana has a long and strong tradition, dating back to the establishment of the first laboratory for experimental cancerology at the Brežice Hospital by Asst. Prof. Dr. Cholewa. Since 2005, the small laboratory with six employees has grown into a modern research group of more than 20 researchers who are successfully implementing the vision of translational oncology, particularly in the fields of electrochemotherapy, gene electrotransfer, bleomycin electro-sclerotherapy, radiobiology, and veterinary oncology. With our commitment to translational research, interdisciplinary collaboration, and the transfer of knowledge into clinical practice, we have made an important contribution to the development of modern oncology therapy in Slovenia and beyond. We successfully completed a phase I clinical study, which demonstrated the safety and efficacy of plasmid gene electrotransfer with IL-12 encoding as part of the SmartGene.si project. In addition to scientific and research work, the department is substantially involved in educational activities and is a part of strong domestic and international networks in the field of biomedical applications of electroporation. We look forward to future collaborative efforts in further developing experimental, translational, and clinical oncology.
Copyright (c) 2025 Gregor Serša , Ajda Medved , Jaka Vrevc Žlajpah , Maja Čemažar https://creativecommons.org/licenses/by/4.0
Two Decades of the Department of Molecular Diagnostics at the Institute of Oncology Ljubljana
The Department of Molecular Diagnostics at the Institute of Oncology Ljubljana was established in 2005 at the initiative of Prof. Dr. Srdjan Novaković. Over the past 20 years, it has evolved into the central national laboratory for genetic testing of individuals with a higher risk of hereditary cancer syndromes, as well as for molecular genetic testing of various types of solid tumours, where tumour genotyping plays a key role in diagnosis, treatment planning, and prognosis. A special area of the department’s work involves pharmacogenetic testing, which identifies patients at increased risk of severe adverse drug effects. In terms of the complexity and quality of its diagnostic services, the Department of Molecular Diagnostics is comparable to internationally recognized centres performing molecular diagnostics. This is demonstrated by its extensive range of tests that follow international clinical guidelines for the management of cancer patients, as well as by its regular participation and successful performance in external quality assessment schemes. As a result, Slovenian cancer patients have access to comprehensive molecular genetic testing within the country, without the need for referral abroad. An important step forward has also been the agreement with the Health Insurance Institute of Slovenia (ZZZS) on the funding of these services, ensuring patients have access to high-quality diagnostics and personalized treatment with targeted therapies, in accordance with the most up-to-date international guidelines and without any additional costs to patients. Patients from healthcare institutions across Slovenia may be referred for molecular genetic testing to the Department of Molecular Diagnostics.
Copyright (c) 2025 Petra Škerl , Srdjan Novaković , Vida Stegel https://creativecommons.org/licenses/by/4.0
Physical activity, muscle, and clinical nutrition
Physical activity and nutrition are inextricably linked in maintaining muscle and overall health, metabolic resilience, and preventing age-related muscle loss. Exercise is a powerful physiological stressor that acutely triggers metabolic, endocrine, and immune responses, posing a major challenge to homeostasis. To better manage this stress, regular exercise induces numerous metabolic adaptations in the body that attempt to reduce it. Metabolic changes triggered by physical exercise include increased energy requirements, adaptation of metabolic fuel use, and hormonal fluctuations. Regular physical exercise leads to structural and functional adaptations at the muscular, cardiovascular, and whole-body levels. Proper nutritional strategies, tailored to the type, intensity, and duration of activity, provide the necessary substrates for work, optimize recovery, promote muscle protein synthesis, and strengthen the immune response. This not only improves athletic performance, but also contributes significantly to the health benefits of exercise, including the prevention and management of many chronic diseases, including some forms of cancer. Since these health benefits are also essential in cancer treatment, knowledge of the principles and application of clinical sports nutrition is becoming increasingly important in oncology. The integration of knowledge in the fields of exercise physiology, metabolic support, and nutritional therapy enables more effective preservation of muscle mass, reduction of metabolic complications, and improvement of response to treatment. The implementation of a clinical sports nutrition approach in oncology practice thus represents an important step towards comprehensive patient care based on scientific evidence and interdisciplinary collaboration.
Copyright (c) 2025 Nada Rotovnik Kozjek, Gašper Tonin https://creativecommons.org/licenses/by/4.0
Summary of the report of the national Registry of Tested Individuals from Families with Hereditary Cancer
Background: In order to facilitate the identification of individuals at high risk for cancer, improve the implementation of genetic testing, and enable effective monitoring of carriers of high cancer risk variants, a national database—the National Registry of Tested Individuals from Families with Hereditary Cancer—was established in 2019. The registry is managed by the Institute of Oncology Ljubljana and is based at the Department of Clinical Cancer Genetics. It includes data on individuals tested for germline pathogenic or likely pathogenic variants (PV/LPV) in genes associated with hereditary predisposition for tumour development. This article presents a summary of the report of the National Registry of Tested Individuals from Families with Hereditary Cancer for the period 2000–2023. Methods: A descriptive statistical analysis was performed, including the analysis of the number of genetic tests performed, the number of individuals tested, and the number of identified germline PV/LPVs in genes associated with hereditary tumour predisposition by year, for the period 2000–2023. Results: From 2000 to 2023, the registry recorded 12,904 tested individuals from 8,781 families. At least one germline PV/LPV in a gene associated with hereditary tumour predisposition was identified in 3,334 individuals from 1,828 families. Thus, a positive genetic test result was found in about one-quarter (26%) of all tested individuals, the majority within the field of hereditary breast and/or ovarian cancer. Conclusion: The collection of data of tested individuals from families with hereditary cancer, together with annual analyses in the form of reports, enables comprehensive monitoring of epidemiological trends—particularly the incidence and prevalence of carriers with hereditary predispositions for tumour development—and facilitates better planning of healthcare for these individuals at the national level.
Copyright (c) 2025 Simona Hotujec , Ana Blatnik , Mateja Krajc https://creativecommons.org/licenses/by/4.0
Optimising patient care in oncology nursing using the McGill Model of Nursing
Background: The McGill Model of Nursing is a holistic, collaborative approach that emphasises the active role of the patient, the involvement of the family and the strengthening of psychosocial support. Although it has been established in the international literature, its implementation in Slovenian clinical practise has not yet been systematically investigated. The aim of this study was to investigate the extent to which oncology nurses apply the principles of the McGill Model, including patient participation, family involvement and psychosocial support. Methods: Approximately 400 nurses working in the field of oncology nursing were invited to participate in this quantitative cross-sectional study. A total of 166 began the questionnaire and 126 completed it in full (response rate 31.5 %). Most of the respondents were female (77.8 %). Their mean age was 37.71 years (s = 8.07), with a mean length of professional experience in oncology nursing of 9.66 years (s = 7.93). The analysis was based solely on fully completed questionnaires. Data was collected using a newly developed scale based on the McGill Model of Nursing and on a five-point frequency and agreement scale. Exploratory and confirmatory factor analyses were performed, as well as Wilcoxon signed-rank tests, Mann-Whitney U tests and Spearman correlations. Results: The factor analysis confirmed a three-factor structure explaining 65.3% of the total variance (KMO = 0.896; Bartlett’s p < 0.001). The empirical medians of all three constructs were significantly higher than the theoretical medians (p < 0.001), suggesting that respondents indicated the use of McGill Model approaches. Participants with access to written protocols or organisational support scored significantly higher (p < 0.001). Moderate to strong positive correlations were found between the use of these approaches and the perceived improvement in the quality of care and the psychosocial well-being of patients (p < 0.001). Conclusion: The results confirm that approaches based on the McGill Model are commonly used in oncological care and are positively associated with perceived improvements in quality of care. This model has the potential for wider and more formalised implementation in the clinical setting in Slovenia.
Copyright (c) 2025 Valentina Masten , Tamara Milić , Matic Petrović , Mirko Prosen , Sabina Ličen https://creativecommons.org/licenses/by/4.0
Cancer burden in Kanal ob Soči Municipality and Goriška Statistical Region (Slovenia) and potential association with environmental pollutants due to waste co-incineration
Background: In the municipality of Kanal ob Soči, residents are exposed to historical asbestos pollution and current emissions from waste co-incineration in a cement plant. This paper discusses the trends over time in the cancer burden with a focus on mesothelioma and assesses the association between environmental pollutants and cancer incidence. Methods: Using data from the Slovenian Cancer Registry, we present the trends in the age-standardised incidence and mortality rates (ASRs) for all cancers (2001–2020) and mesothelioma (2001–2022) in Kanal ob Soči, the Goriška statistical region, and in Slovenia as a whole. We summarise the findings from an umbrella review on the association between cancer and pollutants from co-incineration (1980–2023), and from a descriptive-correlational geographical analysis of cancer risk (all cancers, lung cancer, non-Hodgkin lymphoma and sarcomas) in the 2011–2020 period in relation to the estimated PM10 levels and chromium (Cr) in the soil across four municipalities (Kanal ob Soči, Tolmin, Nova Gorica and Brda). Results: The cancer incidence in Kanal ob Soči is higher than in the Goriška region and in Slovenia as a whole, mainly due to a higher number of mesothelioma cases. However, the ASR remains stable in Kanal ob Soči, while it is increasing in the Goriška region and in Slovenia. The peak of mesothelioma incidence in Slovenia occurred around 2004; from 2014 to 2022, we can observe an annual decline of 3.1%. There is no evidence of an association between cancer and emissions from co-incineration. No links were found with the PM10 or Cr levels. Conclusion: The excess cancer burden in Kanal ob Soči is primarily due to historical asbestos exposure; the impact of waste co-incineration was not confirmed. The developed methodology enables continued environmental impact monitoring. Based on this, we propose some public health measures.
Copyright (c) 2025 Vesna Zadnik, Teja Oblak https://creativecommons.org/licenses/by/4.0
Recommendations for systemic oncological and radiation treatment of the biliary tract cancers
Biliary tract cancers are a rare and heterogeneous group with increasing incidence and high mortality. They have a poor prognosis with an overall survival of less than 1 year. New insights into the molecular genetic heterogeneity of biliary tract cancers and new therapeutic approaches allow these patients to survive longer and have a better quality of life. The Recommendations present the latest recommendations for systemic oncological treatment and radiotherapy of this group of cancers, which, according to international agreements, now include gallbladder carcinoma, intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, with perihilar cholangiocarcinoma and carcinoma of the distal bile duct. The recommendations for systemic treatment are summarized and prepared on the basis of international recommendations, American National Comprehensive Cancer Network (NCCN) and European, European Association for Internal Oncology - European Society of Medical Oncology (ESMO).
Copyright (c) 2025 Erik Brecelj, Martina Reberšek, Ajra Šečerov Ermenc, Vesna Zadnik, Maja Ebert Moltara, Nežka Hribernik, Peter Korošec, Tanja Mesti, Janja Ocvirk, Franci Anderluh, Marko Boc, Marija Ignjatović, Ana Jeromen, Irena Oblak, Vaneja Velenik, Jelena Azarija, Neva Volk, Nena Golob https://creativecommons.org/licenses/by/4.0
Chemotherapy induced peripheral nevropathy (CIPN)
Chemotherapy induced peripheral nevropathy (CIPN) is a dysfunction of the peripheral nervous system as a result of treatment with one or a combination of several cytostatic agents. The most common causative agents of CIPN are taxanes, platinum derivatives and vinca alkaloids, their causative mechanisms of CIPN differ and are related to their cytotoxic activity. CIPN is most often manifested by the sensory symptoms, motor disorders and disorders of the autonomic nervous system are rare. The risk factors for CIPN are general, which we know well and can be limited to a certain extent, while genetic risk factors are currently under intensive research. The pathophysiological processes of the formation of CIPN are partially known, they involve several overlapping mechanisms that cause defects at the level of nerve endings, axonal defects, sensory ganglia disorders, as well as spinal cord injury. Neuro-immune processes are also involved. The diagnosis of CIPN is clinical, specific questionnaires for semi-objective quality of life assessment can be helpful, however the objective method of assessing CIPN is EMG. As a rule, CIPN has a reversible course, but in individual cases we find a chronic irreversible condition. For the treatment of CIPN, non-pharmacological measures are mostly used, and in severe cases also medical support with gabapentin, pregabalin and amitriptyline can be beneficial.
Copyright (c) 2025 https://creativecommons.org/licenses/by/4.0
Recommendations for diagnosis, treatment and follow-up of patients with uveal melanoma
Uveal melanoma is the most common primary malignant intraocular tumor in adults. Uveal melanomas include choroidal melanoma (90%), ciliary body melanoma (6%), and iris melanoma (4%). Between 2017 and 2021, an average of 23 people were diagnosed with uveal melanoma annually in Slovenia, representing 3.7% of all melanomas. The first comprehensive and multidisciplinary treatment guidelines in Slovenia cover choroidal and ciliary body melanomas and are based on the American NCCN guidelines. These recommendations provide a holistic overview of risk factors, clinical presentation, and local treatment options for this cancer, as well as modern approaches to the multidisciplinary management of distant metastases—including the possibility of full blood genotyping for the presence of the human leukocyte antigen (HLA)-A*02:01. The aim of these guidelines is to support specialists from various fields in both communicating with patients and their families, and in choosing the most appropriate treatment options.
Copyright (c) 2025 Barbara Perić, Gregor Hawlina , Vladimir Debelič , Janja Ocvirk , Martina Reberšek , Marko Kokalj, Gaber Plavc , Vesna Zadnik , Alenka Lavrič Groznik https://creativecommons.org/licenses/by/4.0
Pleural, abdominal, and pericardial lymphocytic effusion
Lymphocytic effusion is a complication of several diseases. The main causes of most lymphocytic effusions are malignomas and tuberculosis. Lymphocytes in effusion can be reactive or neoplastic. Reactive lymphocytic effusion develops due to inflammation, systemic and autoimmune diseases, carcinosis, and other rare causes. Malignant lymphocytic effusions are mostly found in patients during the progression of nodal and extranodal lymphomas to the pleural, pericardial or abdominal cavity while effusions caused by lymphomas evolving from serous surfaces are very rare. Cytopathological diagnostic of lymphomas in effusions is based on clinical, morphological, immunophenotypic and molecular features of the disease. According to the international guideless we categorize lymphoproliferative diseases in effusions in five categories: nondiagnostic, benign, atypical cells of undetermined significance, suspicious for malignancy and malignant.
Copyright (c) 2025 Veronika Kloboves Prevodnik , Živa Ledinek , Aleš Rode, Gorana Gašljević https://creativecommons.org/licenses/by/4.0
Neurological adverse events of immune checkpoint inhibitors
The significant beneficial effect of treatment with immune checkpoint inhibitors is relatively often accompanied by adverse events, of which neurological events are rare but can be life-threatening. The article presents neurological complications of treatment with immune checkpoint inhibitors. Two given clinical cases describe neurological adverse events with a clinical picture of peripheral nervous system involvement, namely myositis and acute inflammatory demyelinating polyneuropathy.
Copyright (c) 2025 Nadja Novak Bošnjak, aljoša Andlovic https://creativecommons.org/licenses/by/4.0
The evolution of modern radiotherapy aligns seamlessly with the principles of Citius, Altius, Fortius—faster, higher, stronger— while embracing the Less is More philosophy. In recent years, the 5-fraction radiotherapy regimen has emerged as a transformative approach, offering shorter treatment durations, higher precision, and enhanced therapeutic efficacy, all while optimizing healthcare resources. Evidence from large prospective trials has confirmed its efficacy in breast, prostate, lung, and rectal cancers, as well as in the management of oligometastatic disease. Furthermore, technological advancements in imaging, stereotactic techniques, and dose delivery have played a crucial role in ensuring the safety and precision of these treatments. Beyond clinical efficacy, the benefits of 5-fraction radiotherapy extend to improving patient quality of life, reducing treatment burden, and enhancing healthcare efficiency. In the era of modern radiotherapy, Citius, Altius, Fortius prevails—because Less is More, and the future is now.
Copyright (c) 2025 Angel Montero-Luis, Ivica Ratoša , Helena Barbara Zobec Logar https://creativecommons.org/licenses/by/4.0
A quarter of a century of specialization in medical oncology in Slovenia
Systemic therapy has been shown to improve survival in many cancer patients. The number of anticancer drugs has increased dramatically in recent decades and more than half of all cancer patients are treated with these drugs. The specificity of the disease, the specificity of the treatment, and the drugs, which often have a very narrow therapeutic window, have necessitated the development of a new specialty, medical oncology, separate from internal medicine. Since 2000, medical oncology has been recognized in Slovenia as an independent specialization separate from internal medicine. The incidence of cancer in Slovenia is increasing, and there are more and more patients who need systemic treatment and management by medical oncologists. Unfortunately, the number of oncologists is not increasing at the same rate as the number of patients, and the existing facilities are becoming inadequate.
Copyright (c) 2025 Erika Matos, Simona Borštnar, Cvetka Kuhar Grašič https://creativecommons.org/licenses/by/4.0
Psycho-oncology as part of holistic treatment of cancer patients
When healthcare professionals interact with cancer patients and their families at various stages of their treatment, we also encounter their distress, which is described on a continuum from expectable and transient distress to profound, long-lasting distress that impairs the individual's ability to function and fulfils the criteria for a mental disorder. Through good communication, empathetic support, coping with physical problems, and information, we can significantly support the patient's sources of strength in coping with cancer. It is also important to recognize the patient's level of distress and, if necessary, administer medication and refer them to appropriate support services. A patient who is experiencing severe distress or has a mental health disorder may find it more difficult to participate in communication with healthcare professionals and to cope with the symptoms of physical illness and the side effects of treatment, which may indirectly influence the outcome of treatment for a malignancy.
Copyright (c) 2024 Andreja C. Škufca Smrdel , Jana Markovič, Jana Knific https://creativecommons.org/licenses/by/4.0
Advancing breast cancer circulating tumour cell research at the Institute of Oncology Ljubljana
Circulating tumour cells (CTCs) have become an important biomarker in breast cancer, providing an insight into disease progression and monitoring of therapeutic response. Due to their extreme rarity in blood and the complexity of blood composition, their isolation and characterization is challenging. Specific isolation methods allow the enrichment of CTCs from a blood sample and facilitate further analysis. At the Institute of Oncology Ljubljana, in 2018 we initiated efforts to develop a simple method for the isolation and characterization of CTCs, aimed at identifying these cells through cytopathological analysis. We evaluated two different methods of CTC isolation in breast cancer patients based on different approaches. The first method is based on cell biological properties, such as the expression of the epithelial cell adhesion marker (EpCAM), while the second method is based on physical properties of CTCs, such as their larger size and deformability compared to other blood cells. We found that the physical method is more suitable, as it enables the isolation of higher numbers of morphologically intact CTCs. After isolation, cytological slides are prepared and then characterized by cytopathological analysis and immunocytochemical and immunofluorescence staining. This approach currently allows us to determine the number of single CTCs and CTC clusters in the blood, assess their morphological preservation, and identify their phenotype. In addition to evaluation of single CTCs and CTC clusters in ongoing clinical trials using currently established methods and the planned establishment of a translational platform in mouse models, we aim to expand the range of CTC studies in the future to include genomic and transcriptomic analysis.
Copyright (c) 2024 Tanja Jesenko, Cvetka Grašič Kuhar, Živa Pišljar , Simona Miceska, Veronika Kloboves-Prevodnik , Maja Čemažar https://creativecommons.org/licenses/by/4.0
Efficacy and safety of trastuzumab deruxtecan therapy
Antibody-drug conjugates (ADCs) are a new generation of drugs that currently represent one of the most effective treatment options for cancer. ADCs target a specific target (antigen) that is selectively expressed on a tumour cell. Binding of ADCs to a tumour cell results in targeted intracellular delivery of cytotoxic drugs which causes cell death. An ADC called trastuzumab deruxtecan (T-DXd) has shown remarkable efficacy in several clinical trials called DESTINY. Initial data were available for patients with metastatic HER2-positive breast cancer, followed by data on other HER2-positive solid cancers and breast cancer with low HER2 expression. In this article, we present the first data on the efficacy and safety of T-DXd in Slovenia. We conducted a retrospective study of patients treated with T-DXd at the Institute of Oncology Ljubljana from November 2021 to April 2024. We observed good responses to treatment (objective response 59% in HER2-positive breast cancer, 38% in other HER2-positive solid cancers and 33% in breast cancer with low HER2 expression). After a short median follow-up of 8.8 (95% CI 0.8-33.3) months, real world progression-free survival (rwPFS) was 13 months in HER2-positive breast cancer, 5.8 months in HER2-low breast cancer, and 7.7 months in other HER2 positive or HER2-mutated solid cancers. The safety profile was consistent with that reported in the registration studies, with the exception of pneumonitis, which was reported in a much lower percentage (only 1%). We can conclude that the response rate to T-DXd is high despite the late treatment lines and the heterogeneous population, while rwPFS assessment is unreliable due to the short observation period.
Copyright (c) 2024 Nina Privšek, Simona Borštnar, Cvetka Grašič Kuhar https://creativecommons.org/licenses/by/4.0
Organisation and analysis of genomic counsellors' assessments at the Institute of Oncology Ljubljana in 2023
Introduction: In 2021, the role of genomic counsellor was introduced as a new profile in the Slovenian healthcare system, and likewise at the Institute of Oncology Ljubljana (IOL). In the triage process, clinical genetics specialists determine the number of genetic consultations performed by genomic counsellors, who usually provide counselling for patients who require genetic testing for treatment planning. Methods: We evaluated the data on referrals to genetic counselling and the genetic testing of patients referred to genomic counsellors in 2023. The data were obtained from the database of the Department of Clinical Cancer Genetics at OIL. Descriptive statistical methods and bivariate methods were used for analysing the correlation between variables. Results: In 2023, 2,200 pre-testing genetic counselling consultations were performed. Four genomic counsellors performed 30.4% (669/2.200) of all pre-test genetic counselling consultations. 662 out of 669 patients (i.e. 118 men and 551 women) opted for genetic testing. There were 323 (48%) urgent – fast–track listed patients. The test results of the fast–track listed group were received in 29 (±13) days after the first consultation. In 14.5% (96) of the patients tested a pathogenic/likely pathogenic variant (P/LPV) was identified. The most P/LPVs were found in BRCA1/2 genes (57.3%), followed by the ATM gene (14.6%) and CHEK2 gene (10.4%). Conclusion: Introducing a new profile, a registered nurse with special knowledge in genomic counselling, working as a genomic counsellor, is a successful method of ensuring timely patient care. The additional consultations have helped shorten the waiting times for genetic counselling performed by clinical genetics specialists and speed up the process of genetic treatment for patients.
Copyright (c) 2024 Romana Krivec Matijašič, Tina Kerševan, Mateja Krajc https://creativecommons.org/licenses/by/4.0
Cascade genetic testing in Lynch syndrome families
Introduction: Lynch syndrome (LS) is the most common form of inherited genetic predisposition to colorectal cancer (CRC). LS is caused by a germline pathogenic/likely pathogenic variant (P/ LPV) in one of the mismatch repairs (MMR). Since LS is linked to an increased risk of cancer, it is crucial to test both individuals and their family members (cascade testing). Methods: We performed the analysis of data from the Department of Clinical Cancer Genetics, the Institute of Oncology Ljubljana, i.e. the information on individuals suspected of LS who were referred for genetic counselling between 01/01/2007 and 31/12/2023. The research was conducted using descriptive statistical methods. Results: A total of 246 individuals from 97 LS-positive families were referred for genetic counselling in 17 years. 170 individuals tested positive, representing 69.1% of all individuals tested. 157 family members from 54 families (55.7%) participated in cascade testing. There were 100 women (63.7%) and 57 men (36.3%). In families where the relatives opted for cascade testing, 90 individuals (57.3%) responded within 12 months after the positive result had been disclosed to the first individual tested. On average, 1.6 blood relatives per family participated in presymptomatic testing. In 54 families where relatives opted for testing, the average number of those who decided to test was 2.9 relatives per family. Conclusion: Cascade genetic testing is a successful systematic method for providing genetic testing to blood relatives of P/LPV carriers. In the case of LS, 55.7% of positive families had at least one blood relative opting for cascade testing. In families where relatives underwent cascade testing, an average of nearly three relatives participated, with almost 60% responding within 12 months.
Copyright (c) 2024 Lidija Praprotnik, Simona Hotujec, Barbara Stojanov, Mateja Krajc https://creativecommons.org/licenses/by/4.0
Analysis of assessments at the Department of Clinical Cancer Genetics by cancer site and the importance of genetic findings in treatment planning
Introduction: The Institute of Oncology Ljubljana (IOL) provides genetic assessment for cancer patients who require test results for treatment planning and whenever there is a risk of a hereditary cancer syndrome. In this study, we aimed to analyse the trend of referrals of cancer patients and to assess the pathogenic / likely pathogenic variant (PV/LPV) detection rate in tested individuals according to family history. Methods: In the Department of Clinical Cancer Genetics, IOL, we performed data analysis using descriptive statistical methods and the Microsoft Excel tool. It was based on the number of referrals, patients’ family history data and their genetic test results for germline PV/LPV, focusing on specific cancer site (breast, ovaries, pancreas, and prostate) between 01/01/2020 and 30/06/2024. Results: In a period of 4.5 years, 4,252 patients were referred for genetic counselling, in particular breast cancer patients (3,074). On average, it took 4.3 years from cancer diagnosis to germline genetic testing. 16.5% of all patients tested were diagnosed with germline PV/LPV. Germline PV/LPV were mostly found in ovarian cancer patients (25.2%), followed by pancreatic cancer patients (16.2%), breast cancer patients (16.2%), and prostate cancer patients (11.1%). PV/LPV were most frequent in the genes BRCA1/2. The percentage of patients with a positive family history who tested positive was 19.5%, whereas the percentage of patients with a negative family history was 12.4%. Conclusion: The survey proves the importance of germline genetic testing for cancer patients and their relatives. In fact, 16.5% of patients tested positive for germline PV/LPV and the results were used for treatment planning and prevention. Therefore, it would be reasonable to consider introducing universal genetic testing for certain cancer patients in a safe clinical setting and to be able to identify all those at higher cancer risk.
Copyright (c) 2024 Nina Zavrl, Simona Hotujec, Srdjan Novaković, Mateja Krajc https://creativecommons.org/licenses/by/4.0