Onkologija : Slovenian Journal of Oncology

An overview of recommendations for genetic and preventive management of patients with Li-Fraumeni syndrome

Maša Smrdel — 2026-06-17

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.

Acupuncture in Oncology

Iztok Potočnik — 2026-06-17

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).

Successful genetic testing of a 59-year-old tissue sample

Vita Šetrajčič Dragoš — 2026-06-17

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.

Impact of mean heart dose on mortality after high-dose radiotherapy for lung cancer

Katja Šketa — 2026-06-17

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.

Radiotherapy intensity in patients with advanced solid cancer at the end-of-life

Nena Golob — 2026-06-17

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.

Transcriptomic stratification of advanced primary endometrial tumors by mismatch repair status

Marija Gjorgoska — 2026-06-17

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.

Implantable intrathecal pumps for refractory cancer pain

Teodora Zupanc — 2026-06-17

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.

Comparative analysis of two radiotherapy approaches within total neoadjuvant therapy for high-risk locally advanced rectal cancer

Manuel Ramanović — 2026-06-17

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.

Soft tissue sarcomas

Marko Novak — 2026-06-17

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.

Clinical recommendations for the management of radiodermatitis and radiomucositis

Sandra Gole — 2026-06-17

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.