1. Trametinib-mediated MEK inhibition impairs cancer cell viability and invasion in patient-derived tumor avatars of glioblastoma with extraneural metastases : a proof-of-concept studyMetka Novak, Bernarda Majc, Marija Skoblar Vidmar, Špela Kladnik, Tina Kolenc Milavec, Anamarija Habič, Simona Katrin Galun, Pia Žižek, Andrej Porčnik, Alenka Matjašič, Andrej Zupan, Miha Jerala, Matic Bošnjak, Borut Prestor, Barbara Breznik Vittori, 2026, original scientific article Abstract: Glioblastoma (GBM) remains one of the most lethal human malignancies, yet extraneural metastases are exceptionally rare and poorly understood. Standard treatment—surgical resection followed by chemoradiotherapy—offers only modest survival benefits, and therapeutic options for metastatic GBM are limited. Here, we describe a rare clinical case of metastatic GBM and provide comprehensive molecular characterization alongside a potential targeted treatment strategy. The tumor exhibited several molecular features associated with aggressive behavior, including alterations in the tumor suppressor genes NF1, TP53, PTEN, and RB1, a mesenchymal DNA‑methylation subclass, and activation of the MAPK signaling pathway. To functionally evaluate therapeutic vulnerabilities, we developed tumor models using patient‑derived GBM cells and their assembloids with cerebral organoids that recapitulate patient‑specific tumor biology and the human brain microenvironment. We identified the MEK inhibitor trametinib as a promising candidate capable of selectively reducing viability and invasion of highly aggressive, stem‑like GBM cells within our personalized patient-derived tumor avatars. This work highlights the proof-of-concept evidence that MEK pathway inhibition may represent a potential therapeutic vulnerability to counteract rapid tumor spread and improve responsiveness to temzolomide in this individual metastatic GBM case. Study underscores the need for continued research to advance targeted, multi‑modal therapeutic approaches for GBM.
Keywords: glioblastoma, extraneural metastasis, rare clinical case, organoids, MEK inhibitor, cancer stem cells, cell invasion
Published in DiRROS: 12.08.2026; Views: 53; Downloads: 32
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2. Real-world treatment patterns and outcomes of chemo-immunotherapy with or without radiotherapy in extensive-stage small cell lung cancer : the durvalumab expanded access cohortUrška Janžič, Walid Shalata, Mojca Unk, Ana Sophie Terglav, Natali Shirron, Daher Sameh, Mor Moskovitz, Ofer Merimsky, Patricia Garrido, Miguel Lopes, David Araujo, Talia Shantzer, Hadas Gantz-Sorotsky, Ofer Rotem, Damien Urban, Izabela Chmielewska, Ana Barroso, Alona Zer, 2026, original scientific article Abstract: Purpose: To describe real-world treatment patterns and outcomes among patients with extensive-stage small cell lung cancer (ES-SCLC) treated with first-line chemotherapy plus durvalumab as in CASPIAN trial within Expanded Access Program, with a focus on the use and impact of consolidation (cRT) and salvage radiotherapy (sRT).Patients and methods: This retrospective, multicenter cohort study included patients with ES-SCLC treated with durvalumab plus platinum–etoposide between September 2019 and December 2022 across 11 academic centers in Israel, Poland, Portugal, and Slovenia. Patients characteristics, radiotherapy use, adverse events (AE), and outcomes were collected using a standardized form. Radiotherapy was categorized as cRT, sRT, or palliative RT (pRT). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan–Meier methods and compared using log-rank testing. Multivariable Cox regression evaluated predictors of survival.Results: A total of 133 patients were included (median age 65 years; 74% ECOG PS 0–1). Radiotherapy was administered to 58.6% of patients (cRT 28.2%, sRT 24.3%, pRT 47.4%). Median (m) PFS and mOS for the entire cohort were 6.9 months (m) and 15.9 m, respectively. Patients receiving cRT achieved the longest mPFS (11.7 m) and a mOS of 19.5 m; sRT was associated with an mOS of 20.4 m. Continuation of durvalumab beyond progression combined with RT was associated with improved survival (p = 0.024). Treatment-related AEs occurred in 38.3% of patients, immune-related toxicities were infrequent, and pneumonitis was rare.Conclusion: In this multinational real-world cohort, outcomes with first-line chemo-immunotherapy were consistent with CASPIAN trial. The addition of cRT or sRT appeared feasible, safe, and associated with clinically meaningful survival improvements. Prospective trials are needed to define optimal integration of radiotherapy with chemo-immunotherapy in ES-SCLC.
Keywords: chemo-IO, consolidation radiotherapy, salvage radiotherapy, palliative radiotherapy, ES-SCLC, extensive-stage small cell lung cancer
Published in DiRROS: 11.08.2026; Views: 93; Downloads: 56
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3. Genetic testing for cancer predisposition syndromes in pediatric cancer patientsAnja Urbas, Polona Ušaj, Boštjan Šeruga, Lorna Zadravec-Zaletel, Mateja Krajc, 2026, original scientific article Abstract: Background. Childhood cancer is rare but remains a leading cause of disease-related mortality in children. Unlike adult malignancies, pediatric cancers often arise from inherited or de novo germline variants, with cancer predisposition syndromes (CPS) identified in approximately 7–15% of cases. Recognition of CPS is clinically important, as it affects treatment decisions, surveillance strategies, and family counseling. Materials and methods. Because genetic testing practices for hereditary CPS in pediatric cancer patients vary internationally, we conducted a systematic literature review to summarize current clinical practices and the most recent guidelines for genetic testing in children with cancer. PubMed searches (1994–2025) identified 106 articles; after screening and exclusions, 15 studies were included (13 original studies, one meta-analysis, and one review). Results. Included studies reported cohort sizes ranging from 31 to 3,975 participants, mainly pediatric cancer patients. The number of analyzed genes varied widely (1–1,048). Testing approaches ranged from single-gene testing to multigene panel testing, with multi gene panel testing most commonly used. The prevalence of pathogenic or likely pathogenic germline variants ranged from 2.99% to 47.5%, reflecting differences in cohort composition, gene panel size, and genetic testing methodology. Most guidelines recommend genetic testing based on clinical and biological selection criteria, while universal germline testing is generally not supported, except in Sweden, where whole genome sequencing is offered to all pediatric cancer patients. Conclusions. Phenotype-driven genetic testing currently provides the best resource–benefit balance, although ongoing technological advances may enable broader universal testing in the future.
Keywords: pediatric cancer, cancer predisposition, genetic testing, hereditary cancer
Published in DiRROS: 06.08.2026; Views: 136; Downloads: 40
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4. Decreased gene expression of antiangiogenic factors in endometrial cancer : qPCR analysis and machine learning modellingLuka Roškar, Marko Kokol, Renata Pavlič, Irena Roškar, Špela Smrkolj, Tea Lanišnik-Rižner, 2023, original scientific article Abstract: Endometrial cancer (EC) is an increasing health concern, with its growth driven by an angiogenic switch that occurs early in cancer development. Our study used publicly available datasets to examine the expression of angiogenesis-related genes and proteins in EC tissues, and compared them with adjacent control tissues. We identified nine genes with significant differential expression and selected six additional antiangiogenic genes from prior research for validation on EC tissue in a cohort of 36 EC patients. Using machine learning, we built a prognostic model for EC, combining our data with The Cancer Genome Atlas (TCGA). Our results revealed a significant up-regulation of IL8 and LEP and down-regulation of eleven other genes in EC tissues. These genes showed differential expression in the early stages and lower grades of EC, and in patients without deep myometrial or lymphovascular invasion. Gene co-expressions were stronger in EC tissues, particularly those with lymphovascular invasion. We also found more extensive angiogenesis-related gene involvement in postmenopausal women. In conclusion, our findings suggest that angiogenesis in EC is predominantly driven by decreased antiangiogenic factor expression, particularly in EC with less favourable prognostic features. Our machine learning model effectively stratified EC based on gene expression, distinguishing between low and high-grade cases.
Keywords: endometrial cancer, angiogenic factor, tumour-adjacent tissue, machine learning, TCGA, LEP
Published in DiRROS: 06.08.2026; Views: 94; Downloads: 62
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5. A dual biomarker TK1 protein and CA125 or HE4-based algorithm as a better diagnostic tool than ROMA Index in early detection of ovarian cancerDiana Cviič, K. K. Jagarlamudi, Leon Meglič, Erik Škof, Andrej Zore, David Lukanović, Staffan Eriksson, Joško Osredkar, 2023, original scientific article Abstract: Background: The early detection of ovarian cancer is presently not effective, and it is crucial to establish biomarkers for the early diagnosis of ovarian cancer to improve the survival of patients. Materials and methods: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) in combination with CA 125 or HE4 to serve as a potential diagnostic biomarkers for ovarian cancer. In this study, a set of 198 serum samples consisting of 134 ovarian tumor patients and 64 healthy age-matched controls were analyzed. The TK1 protein levels in serum samples were determined using the AroCell TK 210 ELISA. Results: A combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone in the differentiation of early stage ovarian cancer from the healthy control group, but also a significantly better performance than the ROMA index. However, this was not observed using a TK1 activity test in combination with the other markers. Furthermore, the combination of TK1 protein and CA 125 or HE4 could differentiate early stage disease (stage I, II) more efficiently from advanced-stage (stage III, IV) disease (p < 0.0001). Conclusions: The combination of TK1 protein with CA 125 or HE4 increased the potential of detecting ovarian cancer at early stages.
Keywords: thymidine kinase 1, TK 210 ELISA, TK-liaison, CA 125, HE4, ROMA index, ovarian cancer
Published in DiRROS: 06.08.2026; Views: 84; Downloads: 50
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6. The role of volunteers in supporting the psychosocial well-being of hospitalised children with cancer : a narrative review and recommendations for clinical practiceIvana Kreft, Janez Jazbec, 2026, review article Abstract: Children undergoing cancer treatment face repeated, prolonged hospitalisations carrying substantial risks of psychological distress, social isolation, and impaired development. Volunteers offering structured non-medical activities are widely employed to complement professional psychosocial care in paediatric oncology settings, yet empirical evidence examining their role specifically—as distinct from professionally delivered psychosocial interventions—remains sparse. This narrative review, conducted in accordance with SANRA criteria and drawing on a structured search of PubMed, PsycINFO, and Google Scholar (2000–2025), supplemented by a targeted verification search in July 2026, synthesises the theoretical and preliminary empirical basis for volunteer involvement, critically evaluates associated clinical risks, and proposes evidence-informed recommendations for paediatric oncology clinical practice. Three theoretical frameworks provide the conceptual grounding for volunteer activities: developmental psychological models (Piaget; Erikson), stress and coping theory (Lazarus and Folkman), and the biopsychosocial model (Engel). Indirect empirical evidence—derived predominantly from professionally delivered interventions—supports short-term benefits of structured distraction, play, and social activities on procedural anxiety, pain experience, and sense of social inclusion; the sole study examining volunteer-facilitated activities specifically in paediatric oncology reported meaningful reductions in distress and high family satisfaction. Eight categories of clinical risk are identified, including physical and psychological overload, erosion of child autonomy, suppression of authentic emotional expression, and inadequate coordination with healthcare staff. Six practice recommendations are proposed, centred on a working definition of the volunteer role, mandatory pre-access training, genuine individualisation including cultural adaptation, multidisciplinary-team-led coordination, and structured programme evaluation. Volunteer involvement can meaningfully complement professional psychosocial care when delivered within a structured, supervised, and multidisciplinary-team-coordinated framework. The paediatric oncology team occupies a pivotal role in realising the potential benefits while safeguarding children from associated risks. Prospective research employing standardised volunteer programme definitions and validated child-reported outcome measures is urgently needed to build an evidence base commensurate with the clinical importance of this practice.
Keywords: paediatric oncology, hospitalised children, volunteers, psychosocial support, cancer nursing, play interventions, distraction, clinical recommendations
Published in DiRROS: 06.08.2026; Views: 89; Downloads: 65
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7. Mortality, cancer incidence, and disability among professional drivers in SloveniaAndrea Margan, Metoda Dodič-Fikfak, 2023, original scientific article Abstract: Literature data about all-cause and cause-specific mortality among professional drivers are inconsistent. Most studies report lower all-cause and higher cause-specific mortality. Higher cause-specific mortality is most often the result of malignant and circulatory diseases. The aim of our retrospective cohort study was to get a better insight into the mortality, cancer incidence, and occupational disability of the entire professional driver population in Slovenia (N=8,231) from 1997 to 2016 through standardised mortality ratio (SMR), standardised proportional mortality ratio (SPMR), standardised cancer incidence ratio (SIR), and standardised disability ratio (SDR). Total mortality was significantly lower than that of the general working population (SMR=0.49; 95 % CI=0.44–0.55). When SPMR was calculated, however, the risk of all-cause mortality increased to 1 (SPMR=1.00; 95 % CI=0.89–1.12), of cancer-related mortality to 1.13 (95 % CI=0.94–1.35), and of injury-related mortality to 1.25 (95 % CI=0.97–1.59). Cancer incidence was lower than in the general male working population for all types of cancer (SIR=0.66; 95 % CI=0.59–0.72), lung cancer included (SIR=0.56; 95 % CI=0.41–0.73). Occupational all-cause and cause-specific disability were also lower than in the rest of the working population. Even though all types of cancer and injuries were established among professional drivers in Slovenia, no major risk stand out. However, our findings may have been skewed by the healthy worker effect.
Keywords: healthy worker effect, healthy worker effect, occupational disability, standardised cancer incidence ratio
Published in DiRROS: 04.08.2026; Views: 91; Downloads: 49
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8. Stoma-free survival after rectal cancer resection with anastomotic leakage : development and validation of a prediction model in a large international cohortNynke G. Greijdanus, Kiedo Wienholts, Sander Ubels, Kevin Talboom, Gerjon Hannink, Albert Wolthuis, Francisco B de Lacy, Jérémie H Lefevre, Michael Solomon, Matteo Frasson, 2023, original scientific article Abstract: Objective: To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL). Background: AL after RC resection often results in a permanent stoma. Methods: This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated. Results: This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76). Conclusions: The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies.
Keywords: anastomotic leakage, rectal cancer, rectal cancer resection, stoma-free survival permanent
Published in DiRROS: 03.08.2026; Views: 106; Downloads: 62
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9. European experience on oncological outcomes of patients with early-stage non-small cell lung cancer and any prior cancer following lobectomy or segmentectomy Author links open overlay panelLukadi Joseph Lula, Rita Costa, Lin Huang, Amr Rushwan, Matic Domjan, A.J.P.M. Franssen, Rebecca Weedle, Beatrice Trabalza Marinucci, Clara Forcada Barreda, Črt Jašovič, Tomaž Štupnik, 2026, original scientific article Abstract: Objectives To assess the impact of lung resection extent on early-stage non-small cell lung cancer with a history of any cancer. Methods Retrospective multicentric cohort study including patients with ≤2 cm pathologic size lung cancer with a history of any cancer, operated on from 2015 to 2021 across nine European centers (one per country). Overall survival (OS), disease-free survival (DFS) and lung cancer specific death (LCSD) between both groups were assessed before and after propensity score (PS) −matching. Risk factors for oncologic outcomes were analyzed using parsimonious model cox proportional hazard regression. Kaplan Meier and cumulative incidence function assessed the outcomes. Log-rank test and Gray’ test compared the groups. Linearized risk was used to assess recurrences. Results Of the 1910 patients with early-stage lung cancer patients, 540 (28.2%) had a prior cancer. Lobectomy and segmentectomy were performed in 409 (75.7%) and 131 (24.3%) patients respectively. 5-year OS rates: lobectomy 81.5%, segmentectomy 80.8%, p = 0.8; DFS: lobectomy 76.9%, segmentectomy 74.4%, p = 0.6 and LCSD: lobectomy 8.0%, segmentectomy 4.9%, p = 0.2. These finding were similar in the matched cohort. Locoregional recurrence (linearized risk: lobectomy 0.111, segmentectomy 0.066) and distant recurrence (linearized risk: lobectomy 0.093, segmentectomy 0.055) were not worse in the segmentectomy group. In multivariable analysis, prior cancer negatively impacted only lung cancer specific death HR:1.27 (95%CI:1.00–1.60). Conclusion Compared to lobectomy, segmentectomy has not shown a worse oncologic outcome in patients with history of any prior cancer.
Keywords: segmentectomy, cancer, early-stage, non-small lung, canceroutcome
Published in DiRROS: 27.07.2026; Views: 233; Downloads: 114
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10. Tumor ablation : emerging uses, challenges, and strategic implementationJulie Gehl, Philippe L. Pereira, Colin P. Cantwell, Frédéric Deschamps, Anja Kocijančič, Nina Schmidt, Rok Dežman, Greta Chlebopasevienė, Andreia Roman, Maja Čemažar, Gregor Serša, 2026, review article Abstract: The field of oncology has witnessed remarkable progress with the integration of high-tech innovations in tumor ablation. Tumor ablation therapies, such as radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation (Cryo), irreversible electroporation (IRE), and electrochemotherapy (ECT) have evolved beyond conventional boundaries, offering patients less invasive, highly targeted therapeutic options. Since it works across cancer histologies, tumor ablation is being integrated into cancer care at several levels. Tumor ablation is even considered curative in selected patients with small primary or secondary tumors, e.g. in the liver. Furthermore, it is central in treatment of oligometastatic disease or oligoprogression. Finally, ablation is widely used for symptomatic relief when tumors lead to symptoms affecting quality of life. Knowledge about ablative therapies and their inclusion at multidisciplinary team decision making enables effective and more personalized treatment for patients. This review synthesizes emerging applications of these therapies, focusing on artificial intelligence-driven personalization, robotic-assisted precision, and hybrid models combining ablation with systemic treatments, immunotherapy or targeted drug delivery. It also discusses the infrastructural, educational, regulatory, and ethical challenges that influence the clinical adoption of such treatments. Finally, the review presents strategic recommendations for integrating advanced ablation therapies into healthcare systems while ensuring equity, patient trust, and global accessibility.
Keywords: cancer ablation, high-tech innovations, emerging applications, regulatory issues, ethical issues
Published in DiRROS: 22.07.2026; Views: 181; Downloads: 98
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