Radiology and Oncology (ISSN 1318-2099) is a multidisciplinary journal devoted to the publishing original and high-quality scientific papers and review articles, pertinent to oncologic imaging, interventional radiology, nuclear medicine, radiotherapy, clinical and experimental oncology, radiobiology, medical physics, and radiation protection. Papers on more general aspects of interest to the radiologists and oncologists are also published (no case reports). eISSN: 1581-3207 Journal Metrics Impact factor: 2.2 Five Year Impact Factor: 2.9 Cite Score: 3.7 SJR: 0.618 SNIP: 0.803
License to Publish Please read the terms of this agreement, print, initial page 1, sign page 3, scan and send the document as one file attached to an e-mail to gsersa@onko-i.si Copyright - PDF
Bleomycin ElectroScleroTherapy (BEST): mechanistic parallels to electrochemotherapy, experimental models, and unresolved questions
Background. Bleomycin electrosclerotherapy (BEST) is an emerging treatment option for vascular malformations (VMs), predominantly slow-flow venous malformations, with increasing use in other types of VMs. By combining application of bleomycin with electroporation, BEST enhances intracellular drug delivery and may improve treatment efficacy while allowing the use of lower drug doses. Although clinical evidence supporting its efficacy is growing, the biological mechanisms underlying these effects remain poorly understood. Key unresolved questions include endothelial responses to BEST, what are the dominant mechanisms of vascular injury and remodeling, and how hemodynamics and abnormal vessel architecture affect bleomycin distribution, pharmacokinetics, and effective dosing within the lesion. Although the clinical effects of BEST may be similar to the vascular disrupting effect of electrochemotherapy, it remains unclear whether these vascular mechanisms are in fact the same. Conclusions. Understanding, how bleomycin is delivered, distributed, and retained within VM tissue, and how this interacts with endothelial susceptibility and electroporation efficiency, will be essential for defining optimal dosing strategies. Addressing these questions will require experimental approaches and physiologically relevant models capable of capturing the genetic, structural, and hemodynamic features of VMs. Such advances will be critical for elucidating the mechanisms of BEST and optimizing its clinical application.
Copyright (c) 2026 Barbara Lisec, Maja Cemazar, Tobian Muir, Masa Omerzel, Tanja Jesenko, Bostjan Markelc, Ales Groselj, Rok Dezman, Miha Stabuc, Dimitrij Kuhelj, Gregor Sersa https://creativecommons.org/licenses/by/4.0
Impaired booster-induced SARS-CoV-2 antibody responses in rituximab-treated B-cell lymphoma patients despite peripheral B-cell recovery
Background. Rituximab-treated patients with B-cell lymphoma exhibit profound B-cell depletion and impaired vaccine-induced antibody responses. However, it remains uncertain whether recovery of peripheral B-cell counts after rituximab is sufficient to restore effective humoral immunity following booster vaccination. Patients and methods. In this prospective, single-centre observational study at the Institute of Oncology Ljubljana, adult B-cell lymphoma patients treated with or previously exposed to rituximab received the Comirnaty® mRNA COVID-19 vaccine. Antibody responses to the SARS-CoV-2 spike and nucleoprotein were measured at baseline, 14 days after the second dose, and at 3, 6, 9, and 12 months. A third dose was given at 6 months. T-cell responses (IFN-γ release) were assessed in patients before and after the primary series and booster dose. Lymphocyte subsets were analysed pre-vaccination. Adverse events and nutritional status were monitored. Results. Patients undergoing anti-CD20 therapy showed absent antibody responses. Longer intervals since rituximab correlated with peripheral B-cell repopulation. However, even after reaching normal B-cell counts, patients’ antibody responses after revaccination remained significantly lower than in controls. Conclusion. Rituximab is associated with impaired vaccine-induced antibody responses. Despite recovery of peripheral B-cell counts, patients with B-cell lymphoma show reduced humoral responses compared with healthy individuals following booster COVID-19 vaccination.
Copyright (c) 2026 Tomaž Jurca, Lučka Boltežar, Miha Oražem, Kristina Fujs Komloš, Katka Pohar, Sara Jevnikar, Mario Poljak, Denis Mlakar Mastnak, Nada Rotovnik Kozjek, Bor Vratanar, Janja Ocvirk, Alojz Ihan https://creativecommons.org/licenses/by/4.0
Radiotherapy for malignant spinal cord compression – prognostic factors for better functional outcome
Background. Malignant spinal cord compression (MSCC) is one of the most devastating complications in cancer patients. This retrospective single-center analysis was aimed to identify prognostic factors for better functional outcome after radiotherapy for MSCC. Patients and methods. Consecutive patients with MSCC treated with upfront radiotherapy between January 2017 and December 2022 were included in this analysis. Data on patient, tumor and treatment characteristics, functional status before and after treatment and diagnostic work-up were collected from the hospital digital database. The treatment was considered effective if performance status (PS) was maintained in PS 1-2 patients or PS improved in PS 3-4 patients. Results. 295 patients were treated for MSCC. The most common primary tumor type was lung cancer (29.3%), followed by prostate (18%) and breast cancer (12%). The treatment was effective in 44.7% of patients. Patients who survived more than 1 month after radiotherapy were more likely to experience functional improvement than patients who died within the first month (60.5% vs. 16.5%, p<0.001). In the multivariate analysis PS 1-2, myeloma/lymphoma, MRI at the time of MSCC and no motor deficits vs. paralysis were associated with better functional outcome. Conclusions. The prognosis of patients with MSCC remains poor. Better stratification of patients to assess possible benefit of radiotherapy for MSCC is warranted.
Copyright (c) 2026 Jasna But-Hadzic, Blaz Groselj, Barbara Segedin, Dirk Rades https://creativecommons.org/licenses/by/4.0
Patient doses in image-guided radiotherapy: Status in Europe for CBCT imaging in the pelvic region
Background. Cone-beam CT (CBCT) imaging doses are often neglected in image-guided radiation therapy (IGRT). However, frequent imaging for patient positioning can result in significant and unrecorded additional radiation exposure. This study aims to evaluate clinical imaging doses from kV-CBCT and assess if they are optimized and how, in prostate and pelvic patient positioning protocols across Europe. Materials and methods. Data collected from a survey distributed across Europe on IGRT practices were compiled and analysed. A representative set of imaging protocols were simulated using Monte Carlo based ImpactMC software to assess absorbed doses in various organs in ICRP standard phantom. Absorbed doses to red bone marrow were estimated with a three-parameter mass-energy absorption coefficient method. The simulations were validated against measurements with MOSFET detectors and radiochromic film. Results. Simulated prostate doses ranged from 12mGy to 34 mGy per imaged fraction for pelvic protocols, and 4 mGy to 26 mGy for prostate protocols. The selected length of the imaging region influenced doses to the femur and sacral red bone marrow. Overall, 74% of treatments involved positioning imaging at every fraction, indicating substantial cumulative doses from kV-CBCT imaging. Conclusions. The results of this study suggest that clear guidelines and standardized protocols for CBCT imaging in IGRT are lacking. There is significant potential to optimize the imaging doses. Given that most clinics already perform regular quality assurance for imaging equipment, including dosimetry and positioning accuracy verification, establishing diagnostic reference levels for CBCT imaging in IGRT could help promote further dose optimization.
Copyright (c) 2026 Siiskonen Teemu, Toni Kansanoja, Serhii Brovchuck, Milana Vezirovic , Borislava Petrovic, Antonio Giuseppe Amico, Sonia Sapignolli , Marta Paiusco , Paolo Ferarri , Ana Cravo Sá , Anabela Dias , Pedro Peixoto Teles https://creativecommons.org/licenses/by/4.0
Dosimetric comparison of organs at risk in ultra- hypofractionated (versus hypofractionated postoperative radiotherapy for early breast cancer: single center clinical study
Background: Growing evidence of safety and feasibility has prompted a shift toward ultra-hypofractionated (UHF) schedules in postoperative radiotherapy in early breast cancer. Patients and methods: Eighty patients over 50 years of age with early breast cancer (Т1-2 and N0-1) who underwent postoperative, free-breathing whole breast radiotherapy were included. The investigation group consisted 40 patients who were treated with UHF (26 Gy/5 fx/one week), while data from 40 patients treated with HF (40,5-42,2Gy/ 15-16 fractions/3 weeks) represented the control arm. Dosimetric parameters for OARs (heart and ipsilateral lung) were derived from the dose-volume histograms. Statistical evaluation was done with paired sample t-test and Mann-Whitney U test. Results: Dosimetric analysis revealed that patients treated with UHF schedule received significantly lower equivalent doses in 2 Gy fractions (EQD₂Gy) to OARs compared with those treated with the HF schedule. The mean ipsilateral lung EQD₂Gy dose was significantly lower in the UHF group (3.94 ± 2.1 Gy) than in the HF group (6.24 ± 2.4 Gy; p < 0.01). Among patients with left-sided breast cancer, the mean heart EQD₂Gy dose was also significantly reduced in the UHF group (1.34 ± 0.5 Gy) compared with the HF group (3.02 ± 1.4 Gy; p < 0.01). Conclusion: These findings indicate a consistent dosimetric advantage of the UHF schedule, particularly in reducing radiation exposure to the heart and ipsilateral lung. These results support the dosimetric safety and feasibility of UHF schedules in early breast cancer treatment.
Copyright (c) 2026 Gordana Petkovska, Ivica Ratosa, Valentina Bojovska Trajanovska, Marina Iljovska, Albina Pupakovski Creslovnik , Emilija Lazareva https://creativecommons.org/licenses/by/4.0
Conversion Therapy for Advanced Hepatocellular Carcinoma Following Complete Response to Transarterial Radioembolization Combined with Atezolizumab and Bevacizumab
Background: The current Barcelona Clinic Liver Cancer (BCLC) classification recommends systemic treatment with atezolizumab and bevacizumab as the first-line therapy for advanced hepatocellular carcinoma (HCC). Recent studies suggest that combining systemic immunotherapy with locoregional treatments, such as transarterial radioembolization (TARE), may enhance immune responses and improve overall treatment outcomes. Aim: This article presents a case series of three patients with advanced hepatocellular carcinoma who were treated with transarterial radioembolization followed by atezolizumab and bevacizumab achieving conversion to surgical resection. Material and methods: Between June 2020 and April 2024, three patients with advanced HCC were treated with TARE followed by atezolizumab and bevacizumab. The cohort included: Patient 1: A 59-year-old female,with non-cirrhotic liver, with a 12 cm tumor and a 1,5 cm satellite lesion located in the liver, with hepatic vein and inferior vena cava (IVC) tumor thrombosis (Vv3 classification) and a small lung metastasis. Patient 2: A 63-year-old male with chronic HCV, without cirrhosis, presenting with a 10 cm tumor and portal vein tumor thrombosis (Vp4 classification). Patient 3: A 50-year-old male, Child- Pugh A, with a 17 cm tumor with portal vein and IVC tumor thrombosis (Vp3, Vv3 classification). Results: The combined treatment approach enabled surgical resection in all three patients, each achieving a complete pathological response. Interestingly, follow-up dosimetric analysis showed that all tumors had received a subtherapeutic absorbed radiation doses. Conclusion: In selected patients, combining transarterial radioembolization with systemic immunotherapy may enable conversion to surgical resection in advanced hepatocellular carcinoma, even with subthreshold tumor radiation doses, highlighting a potential synergistic and abscopal effect between locoregional and systemic therapies.
Copyright (c) 2026 Peter Popovic, Ana Kalamutova, Mihajlo Djokic, Anka Cuderman, Gašper Boltežar, Blaž Trotovšek https://creativecommons.org/licenses/by/4.0
HYPER-RAPID PROGRESSION IN SALMONELLA-ASSOCIATED MYCOTIC AORTIC ANEURYSMS: A NARRATIVE REVIEW
Background: Mycotic aortic aneurysms (MAAs), or infective native aortic aneurysms, are rare, life-threatening infections with a high risk of rupture. Non-typhoidal Salmonella (NTS) species show a tropism for the diseased aorta in elderly, atherosclerotic patients, causing explosive growth poorly captured by conventional surveillance. Management is complex when the visceral/paravisceral aorta is involved, making open surgical repair (OSR) risky and requiring tailored endovascular aortic repair (EVAR). This review synthesises evidence on Salmonella-associated MAAs and introduces Hyper-Rapid Progression (HRP) as an early imaging biomarker. Conclusions: Salmonella MAAs represent a high-velocity phenotype. We define HRP as progression from aortitis to aneurysm (≥ 5 mm) within 7 days or rapid enlargement (≥ 5 mm or > 50 %) within 72 hours despite antibiotics. HRP serves as a "red flag" for urgent mechanical stabilisation. While OSR is the gold standard, in anatomically complex or high-risk patients, complex EVAR with parallel grafts and an Optimized Radial Sealing Strategy (ORSS) offers a life-saving alternative. Prospective validation of HRP and its integration into imaging algorithms are needed to improve survival in this devastating condition. Key words: mycotic aneurysm; Salmonella; visceral aorta; hyper-rapid progression; EVAR; ORSS
Copyright (c) 2026 Jernej Lučev, Vojko Flis, Aleš Slanič, Jerneja Čuješ, Silva Breznik https://creativecommons.org/licenses/by/4.0
Between defence and delivery: The DNA sensing response to gene elec-trotransfer
Background. Gene therapy has emerged as a transformative biomedical approach, offering new therapeutic possibilities from many so far uncurable diseases through the introduction of recombinant nucleic acids into target cells. Among non-viral delivery techniques, gene electrotransfer (GET) has become one of the frequently applied methods in clinical trials. It is based on the application of short, high-intensity electric pulses that transiently permeabilize cell membranes and enable the efficient transfer of plasmid DNA or other types of recombinant nucleic acids into various cell types. Beyond its role in gene delivery, GET can trigger complex cellular responses, as the introduced DNA interacts with intracellular DNA sensing pathways involved in innate immunity and inflammation. These responses can influence the therapeutic outcome—either by enhancing antitumour and vaccine-related immune activation or by reducing transfection efficiency when excessive inflammation or cell death occur. Our experimental findings in tumour, muscle, and skin models have shown that even non-coding plasmid DNA delivered by GET can induce local immune stimulation and tissue-specific inflammatory signaling, suggesting that the delivered DNA itself contributes to therapeutic efficacy. Conclusions. The dual nature of cellular responses following plasmid DNA GET represents both an opportunity and a challenge. Controlled activation of innate immunity can be harnessed to amplify antitumour or vaccine efficacy, while excessive responses may hinder applications requiring cell survival and sustained expression. Understanding these mechanisms enables the rational optimization of GET parameters and plasmid vector design to fully exploit the adjuvant effect or reduce the off-target effect of DNA sensing after GET, based on the desired application.
Copyright (c) 2025 Tanja Jesenko, Masa Omerzel, Loree Heller, Maja Cemazar https://creativecommons.org/licenses/by/4.0
QUALITY OF LIFE IN SLOVENIAN PATIENTS WITH SKULL BASE TUMOURS: CROSS-CULTURAL ADAPTATION AND VALIDATION OF A SLOVENIAN SKULL BASE INVENTORY
Background. Skull base tumours frequently manifest as severe physical morbidity and quality of life (QoL) impairment. The disease-related QoL measurement can be performed with disease-specific questionnaires, e.g. Skull base inventory (SBI). Patients and methods...The study consists of two parts: 1.) cross-cultural adaptation and psychometric testing of the Slovenian SBI (SBI-SLO) and 2.) QoL assessment in skull base tumours. Two groups completed the SBI-SLO: 1.) adult patients without prior treatment of anterior, anterolateral and/or central skull base and 2.) healthy controls. Patients with skull-base tumours were further analysed for differences in SBI-SLO total score and domain scores between 1.) benign and malignant tumours and 2.) pituitary macroadenomas and other benign tumours. Results. 59 patients (46% male, 54% female, median age 57,7 years) and 47 subjects from the control group (49% male, 51% female, median age 42,2 years) completed SBI-SLO, which demonstrates an excellent level of internal consistency (Cronbach's alpha = 0.924) and excellent test-retest reliability (ICCA = 0.952). The discriminant validity is confirmed (p = 0.000). SBI-SLO total score, emotional, other and family domain scores were lower in malignant than in benign tumours (p = 0.031, p = 0.038, p = 0.008, and p = 0.046, respectively). Macroadenoma and other benign tumours differ only in neurological domain score (p < 0.05). Conclusions. A skull base tumour, especially malignant, can exert a substantial detrimental effect on a patient's quality of life. The SBI is a key tool for assessing QoL, also available in Slovenian
Copyright (c) 2026 Domen Vozel, Jure Urbančič, Saba Battelino, Nina Božanić Urbančič, Nejc Steiner, Tomislav Felbabić, Roman Bošnjak https://creativecommons.org/licenses/by/4.0
Imaging-Based Prognostic Factors in Patients Undergoing Thermal Ablation for Colorectal Liver Metastases.
Background: To investigate imaging-based prognostic factors in patients who underwent thermal ablation for colorectal liver metastases (CRLM), with a focus on sarcopenia-related body composition parameters and L1-Bone-density in comparison to tumor burden score (TBS). Material and methods: A retrospective analysis was conducted on patients who received thermal ablation for CRLM at our tertiary care center between 2009 and 2023. CT-derived body composition metrics included the psoas muscle volume index (PMVI), the psoas muscle index (PMI), and L1-bone-density. PMVI was automatically extracted using the open-source deep learning tool TotalSegmentator. Comparisons between 1-year survivors and non-survivors were performed using unpaired t-tests. Results: A total of 88 patients were included, most had previously undergone hepatic resection (n=72, 82%). Among sarcopenia-related imaging markers, PMVI showed a significant association with 1-year survival (p = 0.048), with higher PMVI values observed in survivors (mean 113.3 cm³/m³) compared to non-survivors (mean 101.3 cm³/m³). No significant differences were observed for L1-density (p = 0.925) or PMI (p = 0.137). Similarly, the TBS was not significantly associated with 1-year survival (p = 0.182). Conclusion: In our cohort of patients treated with thermal ablation for CRLM, PMVI showed significant association with 1-year survival, which was not observed for conventional tumor burden score or other sarcopenia-related imaging parameters.
Copyright (c) 2026 Maximilian Moos, Fabian Stoehr, Paul Steiner, Lena Maria Jacobi, Tobias Bäuerle, Roman Kloeckner, Constantin Scholz, Hauke Lang, Lukas Müller, Felix Hahn https://creativecommons.org/licenses/by/4.0
INEQUITY IN ACCESS TO PALLIATIVE CARE SERVICES WORLDWIDE AND IN SLOVENIA
Palliative care aims to enhance the quality of life of patients and their families facing progressive and incurable disease by addressing physical, psychological, social, and spiritual challenges. Despite being recognized as a human right, palliative care remains inaccessible to most – only about 14% of those in need receive it. Global demand for palliative care is rising due to aging populations and the increasing burden of chronic diseases. While high-income countries focus on expanding access and inclusivity to this care, low-income countries face severe shortages in prevention, diagnostics and treatment of underlying diseases, which creates an urgent need for palliative care services. Cultural differences, a lack of trained professionals, limited opioid availability, and weak policy further deepen inequities. Historically rooted in religious and charitable care, modern palliative care emerged with Dame Cicely Saunders’ hospice movement, evolving into a medical specialty. Access varies widely – Europe has high integration in some countries but significant disparities in service distribution and opioid use. Africa, Latin America, and parts of Asia still lack widespread provision. In Slovenia, palliative care development began in the 1980s and has recently expanded to include some specialized palliative care services across the country. Despite this progress, palliative care in Slovenia remains underdeveloped due to limited coverage, regional disparities, workforce shortages, insufficient formal education, and lack of a national policy. Opioid availability is slightly below the European average, and its use is declining, which raises concerns about further unmet needs.
Copyright (c) 2026 Nena Golob, Maja Ebert Moltara https://creativecommons.org/licenses/by/4.0
Prostate cancer treatment with Electrochemotherapy (ECT): Safety, efficacy and clinical experience in 144 patients
Background. Prostate cancer (PCa) is a common cancer in men in developed countries. PCa treatment depends on the disease’s stage; focal therapy provides an intermediate approach, with lower toxicity compared to radical prostatectomy, and better tumor control than active surveillance. We report the first retrospective analysis of prostate cancer patients treated with ECT at our institution. Patients and methods. A cohort of 144 men with prostate cancer who were ineligible for or refused standard therapies were included and treated with ECT. Routine follow-up included PSA tests and MRI scans, as well as toxicity and genitourinary function evaluation by means of standard questionnaires. Local response was evaluated with MRI at 3 months after treatment, following the RECIST criteria for solid tumors. Results. The procedure was technically successful in all patients and was well tolerated, with mild and temporary adverse events. Urinary and erectile functions were mostly preserved. A complete response was observed in 75% of evaluated patients, a partial response in 18%, stable disease in 5%, and disease progression in 2%. Short-term response was associated with TNM stage (p<0.05), Gleason score (p=0.0066), and pre-ECT PSA levels (p=0.0070). During follow-up, 18 patients (13%) experienced disease progression; 1-year PFS was 88% (95% CI: 80%-97%) and was found to be significantly associated with tumor stage and pre-treatment PSA levels. Conclusions. ECT is a feasible, safe, and effective treatment for prostate cancer, with extremely low toxicity and side effects. Preliminary results suggest that it offers promising outcomes in terms of local disease control in early-stage tumors, but also in locally advanced cases where other treatments may not be viable.
Copyright (c) 2025 Mara Stevanovic, Mathias Heringer, Mohammad Hjouj, Alessandro Zanasi, Francesca de Terlizzi, Micheal K Stehling https://creativecommons.org/licenses/by/4.0
Invasive properties of patient-derived glioblastoma cells after reversible electroporation in vitro
Background. Electroporation-based therapies are being explored in glioblastoma (GB) treatment, as means of enhancing drug delivery or achieving nonthermal ablation. Yet, little is known about how sublethal exposure affects the invasive behaviour of GB tumour cells. Materials and methods. Five patient-derived GB cell lines were initially screened for intrinsic invasive potential, and two most invasive (NIB140 CORE and NIB216 CORE) were selected for further experiments with electroporation treatment. Cells in suspension were exposed to bursts of high-frequency biphasic electric pulses resulting in electric field strength of 1 kV/cm, which corresponded to conditions of reversible electroporation. Changes in cell invasion and gene regulation were assessed 24 hours after electroporation using transwell assay and RNA transcriptome analysis, respectively. Results. Reversible electroporation at 1.0 kV/cm enhanced invasion in both cell lines. Specifically, the number of invading cells increased by a median of 3.74-fold (274 %) in the NIB140 CORE and by 1.30-fold (30 %) in the NIB216 cell lines. Transcriptomic profiling in NIB140 CORE cell line identified modulation of genes linked to extracellular matrix organization, ion channel activity, and cytoskeletal remodelling, supporting the activation of invasion-related pathways. Conclusions. These findings highlight a potential risk of pro-invasive responses in GB cells surviving within the peripheral zone of electroporation-treated area. The two tested cell lines showed distinct transcriptomic and functional responses, underscoring patient intertumoral heterogeneity. However, given the limitations of 2D cultures, future studies should confirm these effects in more physiologically relevant 3D models such as multicellular spheroids or patient-derived organoids.
Copyright (c) 2025 Anja Blažič, Bernarda Majc, Metka Novak, Barbara Breznik, Lea Rems https://creativecommons.org/licenses/by/4.0
Induction Chemotherapy and Concurrent Chemoradiotherapy for Larynx Preservation in Laryngeal and Hypopharyngeal Cancer
Background. To test the hypothesis that clinical tumor response after a single cycle of induction chemotherapy (ICT) can reliably differentiate between chemo-/radiosensitive and resistant tumors in the larynx preservation setting. Patients and methods..Treatment consisted of docetaxel/cisplatin/5-fluorouracil (TPF) ICT followed by concurrent chemoradiotherapy (cCRT) with weekly cisplatin. The response of the primary tumor was assessed by transnasal endoscopy after the first ICT cycle. Results. 37/39 (95%) patients with laryngeal (46%) or hypopharyngeal (54%) carcinoma responded to one cycle of ICT, and two patients were referred for salvage surgery. Laryngectomy-free survival at 2 and 5 years was 87% and 75%, respectively. The corresponding rates for locoregional control (and also for disease-free survival) were 79% and 70% and for overall survival 92% and 82%. Conclusions. Clinical assessment of tumor response to one cycle of TPF ICT serves as a valid and asy-to-use predictor of tumor sensitivity to platinum-based cCRT.
Copyright (c) 2025 Prof., Assist., Assoc. Prof., Dr., Assist. Prof., Dr., Assist. Prof., Assoc. Prof. https://creativecommons.org/licenses/by/4.0
Human papillomavirus-related oropharyngeal squamous cell carcinoma exhibits enhanced radiosensitivity despite limited activation of cytosolic DNA sensing pathways and innate immune responses
Background. Pharyngeal squamous cell carcinoma (PSCC) is a significant health concern, with human papillomavirus 16 (HPV16) playing a key role in the etiology of oropharyngeal squamous cell carcinoma (OPSCC). HPV16-related OPSCC exhibits enhanced radiosensitivity compared to HPV16-unrelated PSCC, yet the underlying mechanisms remain poorly understood. As HPV16 oncoproteins E6 and E7 are known to interfere with innate immune signalling, we investigated how modulation of cytosolic DNA sensing pathways and innate immune responses changes after irradiation (IR) and whether this contributes to enhanced radiosensitivity in HPV16-related OPSCC. Materials and methods. Using HPV16-related and -unrelated PSCC models, we examined baseline expression levels of DNA sensors and cytokines and assessed the effects of IR on dsDNA accumulation, activation of cytosolic DNA sensors, cytokines, and immune cell infiltration both in vitro and in vivo. Analyses were performed using RT-qPCR and immunofluorescent staining. Results. HPV16-related OPSCC exhibited a distinct baseline expression profile of DNA sensors and cytokines, consistent with suppression of the STING pathway. While IR-induced activation of DNA sensors was dose- and time-dependent across models, HPV16-related OPSCC showed selective activation of cGAS and STING without significant cytokine upregulation or immune activation. In contrast, HPV16-related and unrelated PSCCs displayed activation of multiple DNA sensors, increased cytokine expression, and enhanced immune cell infiltration following IR. Conclusions. The key finding was that the involvement of cytosolic DNA sensing pathways and innate immune system do not increase radiosensitivity of HPV16-related OPSCC. In PSCC models, DNA sensor and cytokine expression varied depending on IR dose and fractionation.
Copyright (c) 2025 Kristina Levpušček, Tanja Jesenko, Tilen Komel, Simona Kranjc Brezar, Gregor Sersa, Maja Cemazar, Primoz Strojan https://creativecommons.org/licenses/by/4.0
Histopathologic Growth Patterns as Prognostic Factor for Survival in Patients with Colorectal Liver Metastases
Background: Histopathologic growth patterns (HGPs) of colorectal liver metastases (CRLM) have emerged as potential prognostic biomarkers, though their clinical significance remains under investigation. The objective is to evaluate the prognostic value of HGPs on recurrence-free survival (RFS) and overall survival (OS) in patients undergoing liver resection for CRLM. Methods: This was a retrospective analysis of the OSLO-COMET randomized controlled trial, where 280 patients underwent laparoscopic or open parenchyma-sparing liver resection for CRLM between February 2012 and February 2016. Patients eligible for long-term analysis and with available histological material were included. HGPs were categorized as desmoplastic, pushing, replacement, or mixed, according to international consensus guidelines. Kaplan–Meier and Cox proportional hazards models were used to evaluate associations between HGPs and survival. Results: A total of 239 patients were included. Desmoplastic HGP was present in 43.5% of patients and associated with significantly better outcomes. Median RFS was 31 months for desmoplastic versus 9, 10, and 11 months for replacement, pushing, and mixed groups, respectively (p = 0.002). Five-year OS was 62% for desmoplastic, 59% for replacement, 55% for mixed, and 39% for pushing HGP (p = 0.036). In multivariable analysis, HGP, lymph node status, and extrahepatic disease were independent predictors of RFS. Age, tumor size, ECOG score, and extrahepatic metastasis significantly impacted OS. Conclusions: Replacement, pushing and mixed HGPs were associated with poor RFS, although replacement and mixed patterns showed better OS after treatment of recurrences. Desmoplastic HGP was independently associated with better RFS and OS following resection for CRLM.
Copyright (c) 2026 Sarkis Drejian, Mehdi Sadat Akhavi, Krzyztof Grzyb, Airazat M. Kazaryan, Åsmund A. Fretland, Bjørn Edwin, Davit L. Aghayan https://creativecommons.org/licenses/by/4.0
Occurrence of clinically relevant thyroid nodules in adults
Background. We aimed to comprehensively investigate the occurrence of thyroid nodules in a nationally representative population as well as in women of reproductive age from a geographic area with adequate iodine intake over the last two decades. Patients and methods. This prospective cross-sectional study included 653 adult participants from three groups: a nationally representative gender-mixed group (205 participants) and women of reproductive age, including non-pregnant (306 participants) and pregnant (142 participants) women. For each participant, demographic data were collected, TSH levels were measured, thyroid volume was estimated, and the presence and size of thyroid nodules were recorded with high-resolution ultrasound. The ultrasound characteristics were analysed. Results. Among the nationally representative participants, nodules were detected in 44.9%, with 39.0% larger than 5 mm and 13.7% larger than 0.5 mL. Among women of reproductive age, nodules were detected in 22.5%, with 14.1% larger than 5 mm and only 2.0% greater than 0.5 mL. The prevalence and size of nodules increased significantly with age in all groups, being significantly lower in non-pregnant women than in pregnant women, who were also older. In non-pregnant women of reproductive age, the number of nodules increased significantly after the age of 25, with the number of nodules larger than 5 mm increasing only after the age of 40. Conclusions. Thyroid nodules are prevalent in the population, but are rarely clinically significant. Therefore, screening for thyroid nodules in asymptomatic individuals with normal thyroid findings on clinical examination should be avoided.
Copyright (c) 2026 Katja Zaletel, Katja Tuta, Tina Ušaj, Katica Bajuk Studen, Nataša Bedernjek Bajuk, Miha Jesenko, Tanja Radevska, Edvard Pirnat, Matej Gregorič, Urška Blaznik, Maša Hribar, Igor Pravst, Simona Gaberšček https://creativecommons.org/licenses/by/4.0
Coronary computed tomographic angiography and atherosclerosis: Prognostic validation of coronary scores in a Slovenian cohort
Coronary computed tomographic angiography and atherosclerosis: Prognostic validation of coronary scores in a Slovenian cohort Tadeja Poropat Flerin1, Borut Jug2, Daniel Košuta2 1Institute of Radiology, University Medical Center Ljubljana, Zaloška 7, 1000Ljubljana, Slovenia 2Department of Vascular Diseases, University Medical Center Ljubljana, Zaloška 7, 1000Ljubljana, Slovenia ABSTRACT Background Coronary computed tomographic angiography (CCTA) provides information on coronary atherosclerosis burden and extent. In the present analysis, we compared the prognostic impact of coronary scores (maximal coronary stenosis, segment involvement score [SIS] and segment stenosis scores [SSS], and the CCTA-modified Duke score). Methods We retrospectively reviewed CCTA images of patients with suspected coronary obstruction and excluded patients who underwent planned revascularisation. Using Cox multivariate analysis, we estimated the hazard ratio (HR) with 95% confidence intervals (CI) for different coronary scores to predict death, myocardial infarction, and late unplanned revascularisations (as individual and composite endpoints). Model performance was evaluated using area under time-dependent receiver operating characteristic curves (AUC). Results We included 750 patients (median age 61 years, 54% women) with a median followup 1,465 days. Unadjusted HR for major cardiovascular events ranged from 3.87 (95%CI 1.49-10.0, p=0.005) for obstructive disease (>50% stenosis in any vessel) to 1.17 (1.09-1.25, p<0.001) for SIS (each additional segment involved). Predictions remained significant for all endpoints and after adjusting for coronary artery calcium score and risk factors. Area under curve (AUC) for coronary stenosis was 0.77 (95%CI 0.71-0.82), for SIS was 0.77 (95%CI 0.72-0.83), for SSS was 0.77 (95%CI 0.71-0.82), and for Duke score was 0.67 (95%CI 0.61-0.74). Conclusion Our study has confirmed that coronary atherosclerosis burden and extent independently predict major cardiovascular events in patients who had undergone CCTA, but were not referred for invasive diagnostic procedures and revascularisation
Copyright (c) 2026 Tadeja Poropat Flerin, Borut Jug, Daniel Košuta https://creativecommons.org/licenses/by/4.0
Interactions between hematological biomarkers of virus infection and immune cells in mediating distant metastasis in nasopharyngeal carcinoma: Insights into prognosis and induction chemotherapy administration
Abstract Background and purpose: Considering the increased metastatic risk in hepatitis B surface antigen (HBsAg)-positive patients with nasopharyngeal carcinoma (NPC), we aimed to investigate the interactions among HBsAg, tumor burden indicators, and immune function in the accurate stratification of prognosis and treatment for this specific cohort. Methods: We retrospectively analyzed 1650 pathologically-confirmed patients with NPC from two centers and performed interaction and mediation analyses among HBsAg, plasma Epstein–Barr virus (EBV) DNA load, and absolute lymphocyte count (ALC), concerning distant metastasis. A 1:1 random matched-paired analysis was performed to evaluate survival according to risk and treatment stratification. Treatment-related adverse events were also compared. Results: Overall, 17.3% (285/1650) of patients tested positive for HBsAg. Significant interactions occurred between HBsAg and low ALC (≤ 1.9×109/L) (HL), as well as between HBsAg and high plasma EBV DNA load (> 4000 copies/mL) (HE), both independently predicting poor distant metastasis-free survival (DMFS). The influence of T and N staging on tumor metastasis was mediated by HL (+) and HE (+), respectively. Among patients with stage III–IVa NPC, interaction associations presented with a worse 5-year DMFS and higher rates of severe neutropenia and leukopenia among those treated with additional induction chemotherapy (IC) than among those treated with radiochemotherapy alone. Conclusions: Interactions exist between HBsAg positivity and high EBV/low ALC, mediating the effects of tumor staging and distant metastasis. The collective influence of viral infection, tumor burden, and reduced immune cells leads to worse DMFS in patients with HBsAg-positive NPC, requiring a tailored treatment beyond IC.
Copyright (c) 2026 Shuqi Li, Biyun Chen, Di Cao, Chao Luo, Zhiying Liang, Kit Ian Kou, Ge Ren, Wenjie Huang, Guangying Ruan, Lizhi Liu, Haojiang Li, Siyu Zhu, Fei Ai https://creativecommons.org/licenses/by/4.0
Anlotinib Monotherapy in Recurrent or Metastatic Nasopharyngeal Carcinoma: A Multicenter Case-Series Analysis
Background: Anlotinib has shown encouraging therapeutic effect on various solid tumors. The effect of anlotinib in the treatment of patients with recurrent or metastatic nasopharyngeal carcinoma remains unclear. This study assessed the efficacy and safety of anlotinib monotherapy in rmNPC patients. Methods: We retrospectively recruited 30 patients with rmNPC, most following at least one previous line of systemic therapy. Patients underwent anlotinib monotherapy (12 or 10 mg/day). The primary endpoint was objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: Thirteen patients (43.3%) had metastatic NPC, 10 (33.3%) had recurrent NPC, and 7 (23.3%) had both. Twenty-two patients (73.3%) were platinum-refractory, and 23 (76.7%) received at least three anlotinib cycles. The best overall response was observed in four patients with partial response, stable disease in 18, and progressive disease in eight. The ORR was 13.3% (95% confidence interval [CI], 0.4–26.2%) and disease control rate was 73.3% (95% CI, 56.5–90.1%). The median OS and PFS were 11.5 (95% CI, 7.5–15.5) and 5.7 (95% CI, 4.7–6.7) months, respectively. Multivariate analysis showed that liver metastases (hazard ratio, 7.907; 95% CI, 2.613–23.923, P < 0.001) significantly affected the PFS. The relatively common ≥ Grade 3 adverse reactions were hand-foot syndrome (13.3%) and oral mucositis (13.3%). Conclusion: Anlotinib monotherapy demonstrated positive efficacy in patients with rmNPC. It was well tolerated by these patients and had limited toxicity.
Copyright (c) 2025 Wei Jiang, Guanjie Qin, Guanjie Qin, Yixin Su, Yong Liang, Bin Zhang, Yufei Pan, Jianxun Lu, Yueyun Xie, Jinxuan Dai, Kequan Chen, Fengfei Qin, Huiyun Yang, Xiangyun Kong, Yuan Xie, Xiaolan Xiaolan , Yunyan Mo, Ruyun Zhang, Jian Zhang https://creativecommons.org/licenses/by/4.0
Baseline and dynamic changes in skeletal muscle mass as predictive biomarkers in patients with metastatic renal cell carcinoma treated with Nivolumab
Background: Sarcopenia, defined as a loss of skeletal muscle mass and function, has been increasingly recognized as a negative prognostic factor in oncology. This study aimed to investigate whether sarcopenia, evaluated both before and during immunotherapy, could predict treatment response and survival in patients with metastatic renal cell carcinoma (mRCC) treated with Nivolumab. Materials and methods: This retrospective cohort study included 50 mRCC patients who received Nivolumab between 2019 and 2022 and underwent abdominal computed tomography (CT) before and after treatment. Sarcopenia was assessed by calculating the skeletal muscle index (SMI) at the third lumbar vertebra using standard Hounsfield unit thresholds (−29 to +150 HU). Treatment response was evaluated according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier curves and Cox regression models. Results: Sarcopenia was identified in 60% of patients and was significantly associated with multiple organ metastases (p = 0.003). Patients with sarcopenia or a negative change in SMI during treatment demonstrated poorer treatment response (p = 0.027 and p = 0.021, respectively). Both OS and PFS were significantly shorter in sarcopenic patients and those with declining muscle mass. Conclusions: Pre-treatment sarcopenia and muscle loss during immunotherapy were independently associated with inferior survival and treatment response in mRCC patients receiving Nivolumab. Sarcopenia may serve as an imaging-based prognostic biomarker in this population. Keywords: Renal cell carcinoma; Sarcopenia; Nivolumab; Prognosis; Immunotherapy; Computed tomography
Copyright (c) 2025 Erdem Özkan, Murathan Köksal, Bünyamin Ece, Mustafa Koyun, Ömer Faruk Kuzu, Yusuf Açıkgöz, Efnan Algın https://creativecommons.org/licenses/by/4.0
Genetic variability of HIF1A and response to treatment with cisplatin in combination with pemetrexed or gemcitabine in patients with malignant mesothelioma
Background. Treatment of malignant mesothelioma (MM), still relies on chemotherapy with cisplatin in combination with pemetrexed or other drugs. Studies indicate that hypoxic conditions within tumour tissue reduce responsiveness to cisplatin-based chemotherapy. Cellular adaptation to hypoxia occurs through intracellular proteins from the hypoxia-inducible factor (HIF) family, which exist in three isoforms, with only the HIF-1 isoform being expressed in all cells. HIF-1 consists of the regulatory alpha subunit (HIF-1A) and constitutively expressed beta subunit (HIF-1B). Single nucleotide polymorphisms (SNPs) of HIF1A gene may influence its function under hypoxic conditions within the tumor tissue of MM, potentially altering the response of MM to platinum-based chemotherapy. The aim of our study was to investigate the role of HIF-1A in the response to chemotherapy in patients with MM. Patients and methods. We conducted a retrospective association study that included 234 patients with MM, who were treated at the Institute of Oncology Ljubljana between January 2001 and September 2018 with a combination of cisplatin/pemetrexed or cisplatin/gemcitabine. Selected HIF1A SNPs (rs1154965, rs11549467, and rs2057482) were determined using the competitive allele-specific polymerase chain reaction (KASP). Additionally, we used the Taqman assay for independent confirmation of rs11549465 genotyping results obtained with KASP. The impact of the SNPs on response to chemotherapy was analysed using logistic regression. For survival analysis, we used the Kaplan-Meier method and Cox regression. All tests were two-tailed. Results. In heterozygotes with the HIF1A rs11549465 CT genotype, response to chemotherapy was statistically significantly worse compared to homozygotes with the CC genotype, but only with the adjustment for weight loss and CRP (ROadj = 0.37; 95% CI = 0.14–0.97; Padj = 0.044). The SNPs rs11549467 and rs2057482 were not associated with response to chemotherapy (P > 0.05). None of the investigated SNPs were associated with progression-free survival (PFS) (P > 0.05) or overall survival (OS) (P > 0.05). Conclusions. In patients with the HIF1A rs11549465 CT genotype, we found a statistically significantly worse response to chemotherapy compared to the CC genotype with the adjustment for weight loss and CRP. SNPs rs11549467 and rs2057482 were not associated with response to chemotherapy in MM. None of the investigated polymorphisms were associated with PFS or OS in MM chemotherapy treatment. The findings of this study will increase our understanding of the role of HIF1A polymorphisms in MM and may offer valuable insights into their impact on other cancers as well.
Copyright (c) 2025 Matic Setina, Eva Setina, Ziga Doljak, Katja Goricar, Vita Dolzan, Viljem Kovac https://creativecommons.org/licenses/by/4.0
Radiation-Induced Impairment of Skeletal Muscle Regeneration
Radiotherapy is a cornerstone of treatment for various cancers, but often causes collateral damage to surrounding healthy tissue, including skeletal muscle. Ionizing radiation leads to oxidative stress and inflammation, which impairs the regenerative capacity of muscle tissue. Irradiation reduces the number and functionality of satellite cells and disrupts the tightly regulated processes of myogenesis and tissue remodelling. In addition, irradiation alters the muscle microenvironment by promoting fibrosis and vascular damage, which further impedes effective regeneration. Cytokine signalling pathways are also dysregulated following irradiation, contributing to impaired activation and differentiation of satellite cells. There is also evidence that factors such as melatonin and growth factors can improve muscle regeneration. Understanding the molecular and cellular mechanisms underlying the impairment of muscle regeneration after radiotherapy is crucial for the development of targeted strategies to mitigate side effects and improve patients' quality of life. Overall, the preservation and restoration of muscle function in irradiated tissue remains a critical challenge that requires multidisciplinary approaches.
Copyright (c) 2025 Maja Čemažar, Mihaela Jurdana https://creativecommons.org/licenses/by/4.0
FCGBP inhibits the development of LSCC and cisplatin resistance through the PIGR/JAK2/STAT3 pathway
Background: The second most prevalent cancer in the head and neck is laryngeal squamous cell carcinoma (LSCC), and one of the main treatment challenges is cisplatin resistance. In addition to being a tumor suppressor in many types of cancer, IgGFc binding protein (FCGBP) is linked to tumor medication resistance. We looked into the function of FCGBP in LSCC in this work. Method: FCGBP expression and prognostic analysis were analyzed by GEPIA website. The effects of FCGBP in vivo were validated using the nude mouse xenograft model of mouse LSCC, while the effects of FCGBP in vitro were investigated using half maximal inhibitory concentration (IC50) analysis, colony formation assay, and flow cytometry assay. The mechanism by which FCGBP inhibits cisplatin resistance was studied by knocking down polymeric immunoglobulin receptor (PIGR). Result: FCGBP is lowly expressed in head and neck squamous cell carcinoma and LSCC cell lines and is associated with poor prognosis. FCGBP can inhibit the viability and proliferation of LSCC cells, and FCGBP can inhibit the resistance of LSCC cells to cisplatin. In addition, FCGBP can regulate the PIGR/JAK2/STAT3 pathway and exert anti-cancer and anti-cisplatin resistance effects through this pathway. In addition, FCGBP can inhibit the growth of LSCC tumors in vivo. Conclusion: Our findings demonstrated that the FCGBP/PIGR/JAK2/STAT3 axis plays a regulatory role in cisplatin resistance in LSCC, indicating that FCGBP could be a viable target to enhance the therapeutic benefit of cisplatin.
Copyright (c) 2026 Xuemei Wan , Yunlan Zeng, Ming Xiong, Lin Chen, Yundan Bai https://creativecommons.org/licenses/by/4.0
The implementation of a robotic surgical plat-form for the treatment of patients with malig-nant or pre-malignant pancreatic tumors at the University Medical Center Ljubljana
Background. Robotic platforms are increasingly employed in the field of minimally invasive pancreatic surgery. It is essential to develop an innovative method that ensures both safety and efficacy, producing outcomes comparable to those of established treatment modalities. Implementation process should incorporate surgical science, education, local implementation, and non-technical skills. In our study, we describe the safe implementation of a robotic platform in pancreatic surgery within our medical institution. Patients and methods. We analysed prospectively collected data from the first ten consecutive robotic-assisted distal pancreatectomies (RDP) and pancreatoduodenectomies (RPD). Due to nature of the study no statistical analysis were performed. Results. The mean operating time was 211minutes (±49.4) for RDP and 365 minutes (±69.6) for RPD, with blood loss 330 mL for RDP and 195 mL for RPD. Hospital stay was 8.7 days (±3.9) in RDP and 7.9 days (±3.9) in RPD. One patient (10%) in the RDP group developed CR-POPF and DGE. The mean tumour size was 31 mm (±9.8) in the RDP and 27 mm (±7.5) in the RPD. The mean number of lymph nodes harvested was 6 (0–24) in the RDP and 15 (6–22) in the RPD. The R0 resection rate was 60% in the RDP and 70% in the RPD. Conclusions. Robotic surgical technology can be safely and effectively integrated into a clinical setting. This integration should be facilitated through a well-established training program and curriculum. Nonetheless, patient selection is important, especially in the early phases of robotic program development.
Copyright (c) 2025 Miha Petrič, Patricio Marcelo Polanco, Jan Grosek, Aleš Tomažič, Blaž Trotovšek, Boštjan Plešnik https://creativecommons.org/licenses/by/4.0
The role of focal adhesion kinase in bladder cancer: translation from in vitro to ex vivo human urothelial carcinomas
Background. Focal adhesion kinase (FAK), a cytoplasmic tyrosine kinase, plays a crucial role in focal adhesion turnover by interfacing between the extracellular space, transmembrane integrins, and actin filaments. Its significance for the progression of several malignancies, including bladder cancer, has been well-documented. However, its precise role and the implications of its inhibition in bladder cancer tissues and urothelial in vitro models has not been fully explored. This study examined FAK expression and function in human bladder cancer biopsies and in vitro bladder cancer models. Materials and methods. Ex vivo analyses were performed using reverse transcription-quantitative PCR (qRT-PCR), western blotting, and immunohistochemistry to compare FAK expression between bladder cancer tissues and adjacent normal tissues. In vitro, FAK expression was assessed in urothelial cancer cell lines RT4 and T24 and normal porcine urothelial (NPU) cells using qRT-PCR and western blotting, as well as flow cytometry for the quantification of FAK-positive RT4 and T24 cells. The role of FAK in cancer cell survival was explored in vitro using microRNA (miRNA) to silence FAK expression. Additionally, we used FAK inhibitors PND-1186, PF-573228 and defactinib to investigate the effects of FAK inhibition on normal compared to cancerous bladder urothelial cells. Results. Ex vivo analyses demonstrated significantly higher FAK expression in bladder cancer tissues compared to adjacent normal tissues. Similarly, in vitro analyses showed significantly higher FAK expression in urothelial cancer cell lines RT4 and T24 than NPU cells. Silencing FAK using anti-FAK plasmids led to increased caspase-3-mediated apoptosis of RT4 and T24 cells and growth reduction of stably transfected T24 cells. Importantly, based on cell viability assays, treatment with 100 μM defactinib for 2 hours per day on 3 consecutive days was identified as a clinically relevant regimen. Under this treatment, the viability of differentiated NPU cells remained high at 108.4 ± 17.1%, while the viability of 2-day RT4 and 2-day T24 cells was drastically reduced to 4.1 ± 2.7% and 7.6 ± 2.9%, respectively. Conclusions. To our knowledge, this is the first report demonstrating the role of FAK and its inhibition across both normal and cancerous bladder urothelial models. This study highlights the critical role of FAK in the progression of human bladder cancer and establishes a foundation for exploring FAK inhibition as a potential therapeutic approach in bladder cancer treatment.
Copyright (c) 2025 Gaja Markovič, Nataša Resnik, Aleksandar Janev, Daša Zupančič, Gašper Grubelnik, Maruša Debeljak, Maja Čemažar, Tanja Jesenko, Maša Omerzel, Tomaž Smrkolj, Mateja Erdani Kreft https://creativecommons.org/licenses/by/4.0
Heterogenous mitochondrial ultrastructure and metabolism of human glioblastoma cells: differences between stem-like and differentiated cancer cells in response to chemotherapy
Background: Glioblastoma stem-like cells (GSCs) contribute to the resistance of glioblastoma (GBM) tumors to standard therapies. The background of the resistance of GSCs to the chemotherapeutic agent temozolomide is not yet fully understood in the context of cellular metabolism and the role of mitochondria. The aim of this study was to perform a detailed ultrastructural characterization of the mitochondria of GSCs prior and post temozolomide exposure and to compare it to differentiated GBM cells. Methods: Patient-derived and established GBM cell lines were used for the study. The ultrastructure of the mitochondria of the examined cell lines was assessed by transmission electron microscopy. The microscopic analysis was complemented and compared by an analysis of cell metabolism using Seahorse extracellular flux analysis. Results: We found that the metabolic profile of GSCs is quiescent and aerobic. Their elongated mitochondria with highly organized cristae is indicating increased biogenesis and mitochondrial fusion and corresponds to a more OXPHOS-dependent metabolism. The metabolism of GSCs is dependent on OXPHOS and there are no changes in defective mitochondria fraction after the treatment with temozolomide. In contrast, differentiated GBM cells with fragmented mitochondria, which have less organized cristae, are more energetic and glycolytic. Temozolomide treatment induced significant ultrastructural mitochondrial damage in differentiated GBM cells. Conclusions: We demonstrated differences in mitochondrial ultrastructure and cellular metabolism between GSCs and differentiated GBM cells in response to temozolomide, suggesting that mitochondria play an important role in the resistance of GSCs to temozolomide. This study provides a basis for further studies addressing GSC chemotherapy resistance in the context of mitochondrial structure and function.
Copyright (c) 2025 Urban Bogataj, Metka Novak, Simona Katrin Galun, Klementina Fon Tacer, Miloš Vittori, Cornelis J.F. Van Noorden, Barbara Breznik https://creativecommons.org/licenses/by/4.0
Breaking the Pain Barrier: Implantable Intrathecal Pump Therapy as a Game-Changer in Cancer Pain Management
Chronic cancer pain, especially in advanced stages, remains a significant clinical challenge, often necessitating complex multimodal strategies. Although systemic opioids are standard therapy, many patients experience inadequate relief or adverse effects. Implantable intrathecal drug delivery systems (IDDS) have emerged as a promising alternative, enabling targeted analgesia with reduced opioid burden and improved quality of life. This narrative review summarizes current evidence on the clinical application, efficacy, safety, and cost-effectiveness of IDDS in cancer pain management. Literature sources include clinical trials, observational studies, health-economic evaluations, and international guidelines published between 2002 and 2023. A Slovenian case report is included, detailing the first national experience with IDDS implantation for refractory cancer pain. Clinical outcomes were assessed using the Visual Analogue Scale (VAS), EORTC QLQ-C30, and the revised Edmonton Symptom Assessment System (r-ESAS). Findings from the literature confirm that intrathecal pumps provide substantial and sustained pain relief, often with a significant reduction in systemic opioid doses and associated side effects. Compared to conventional pharmacotherapy, intrathecal delivery is associated with improved patient-reported outcomes, fewer hospitalizations, and lower long-term healthcare costs. In the Slovenian case, VAS scores decreased from >8 to 3 shortly after implantation, with parallel improvements in quality-of-life indices. IDDS represent a clinically effective and economically sustainable option for selected patients with complex cancer pain, particularly when systemic therapy proves insufficient. Their integration into multidisciplinary palliative care pathways supports personalized, safe, and compassionate treatment approaches. By combining an evidence-based overview with real-world national experience, this review underscores the therapeutic value of intrathecal drug delivery and calls for broader clinical awareness and future research.
Copyright (c) 2025 Iztok Potocnik, Branka Stražišar, Helena Lenasi, Teodora Zupanc https://creativecommons.org/licenses/by/4.0
Dual-channel ultrasonic images empowered deep learning: significantly improving prediction of occult central lymph node metastases in solitary papillary thyroid microcarcinoma
Background. Central lymph node metastasis (CLNM) significantly elevates the risk of postoperative recurrence and contributes to ongoing debates regarding the necessity of prophylactic dissection in clinically node-negative papillary thyroid microcarcinoma (PTMC). Therefore, accurate preoperative prediction of occult CLNM is crucial for tailoring individualized treatment strategies Patients and methods. This retrospective study included 461 patients with PTMC from two hospitals who underwent preoperative ultrasound. A dual-channel deep learning (DL)model was developed by combining longitudinal and transverse ultrasound images. The model’s performance was compared with single-direction DL models and a clinical model using machine learning classifiers. Performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves. Results. The dual-channel DL model outperformed the single-direction models, with AUC values of 0.765 in the training set and 0.726 in the external test set. The combined model, which integrated DL features and clinical indicators, achieved the highest AUC of 0.900 in the training set and 0.873 in the external test set, surpassing both the DL_F and clinical models. Conclusions. The dual-channel DL model demonstrated superior performance in predicting occult CLNM in PTMC patients. When combined with clinical features, it offers a robust tool for personalized risk stratification and treatment decision-making, providing a non-invasive method for predicting occult CLNM and supporting individualized treatment strategies.
Copyright (c) 2026 Long Liu, Meihua Li, Chao Jia, Gang Li, Qiusheng Shi https://creativecommons.org/licenses/by/4.0
Efficacy and safety of percutaneous microwave ablation for liver tumors using an antenna with anti-phase technology offering ultraspherical ablation
Background. Anti-phase technology, a novel advancement in microwave antennas for percutaneous liver ablations, forms more spherical ablation zones. This study aimed to evaluate the efficacy and safety of microwave ablation (MWA) treatment for liver tumors using a microwave antenna equipped with anti-phase technology. Patients and methods. The study included 92 patients (133 lesions) treated with MWA for hepatocellular carcinoma (HCC) or liver metastases. Of these, nine patients had HCC, and 83 had metastases (46 colorectal and 37 non-colorectal metastases). Retrospective analysis was conducted on patients’ age, sex, pre- and post-procedural laboratory values (white blood cell count, neutrophil-to-lymphocyte ratio), tumor and ablation zone dimensions (pre-procedure and post-procedure day 1 and months 1, 3, and 6), details of the single-shot MWA procedure (duration, power output), procedure-related complications, and local progression/recurrence during follow-up. Results. The technical success rate of MWA was 100%. Ablations were performed at a median power output of 80 watts (range: 50–100), and the mean ablation duration was 5.2±2.1 minutes. Follow-up imaging revealed an ablation zone diameter-to-tumor diameter ratio of 1.63±0.3. Major complications occurred in three patients (3.2%) and included liver abscess (n=1/92), hemorrhage (n=1/92), and pleural effusion (n=1/92). Minor complications were observed in 29 patients (31.5%). The median follow-up time of the patients was 33 (range 10–36) months. The median disease-free survival time was 25 months (95% confidence interval: 21–27). During the 24-month follow-up, local tumor progression occurred in 39 patients (42.4%). Tumor size was identified as an independent risk factor for local progression (p=0.012). Conclusions. This study represents the longest follow-up duration and the largest patient cohort for the MWA treatment of liver tumors using anti-phase technology. The results demonstrated high technical success and acceptable local control and complication rates.
Copyright (c) 2025 Erbil Arik, Onur Taydas, Tunahan Dertli, Omer Faruk Sevinc, Ahmet Burak Kara, Omer Faruk Topaloglu, Mustafa Ozdemir, Adem Senturk, Alp Omer Canturk, Ilhan Hacibekiroglu, Mehmet Halil Ozturk https://creativecommons.org/licenses/by/4.0