1. Primary vitreoretinal lymphoma : diagnostic and therapeutic insights from a Slovenian population-based studyNika Vrabič, Lučka Boltežar, Matej Panjan, Veronika Kloboves-Prevodnik, Polona Jaki Mekjavić, Marija Skoblar Vidmar, Pia Klobučar, Mojca Globočnik Petrovič, Nataša Vidović Valentinčič, 2026, original scientific article Abstract: Background: This study aimed to determine the national incidence, characterize clinical features, and evaluate the treatment outcomes of primary vitreoretinal lymphoma (PVRL) in Slovenia. Methods: We conducted a population-based, retrospective case series of all patients diagnosed with PVRL at the Eye Hospital, University Medical Center Ljubljana, between January 2013 and May 2024. The diagnosis was histopathologically confirmed, and primary central nervous system involvement was excluded. Clinical presentation, diagnostic delay, treatment modality, and adverse events were analyzed. Progression-free survival (PFS), overall survival (OS), and lymphoma-specific survival (LSS) were calculated. Results: Twelve patients were diagnosed with PVRL (four men, eight women; median age of 76 years). The average annual incidence was 0.52 cases per million. The median time from symptom onset to diagnosis was 238 days. The two most common symptoms were decreased visual acuity (75%) and floaters (58%). Vitreous cellular infiltration was the predominant clinical sign and was observed in 92% of patients. Five patients presented with unilateral disease, seven with bilateral disease, and three with unilateral disease that progressed to bilateral involvement. The median follow-up was 31.5 months. Eleven patients received one or more treatment modalities: intravitreal rituximab and/or methotrexate, local radiotherapy, and/or systemic chemotherapy. Local remission was achieved in all treated eyes. Two cases of granulomatous uveitis occurred during intravitreal rituximab therapy. The median PFS was 12 months; the two- and three-year PFS rates were 37.5% and 18.8%, respectively. The median OS was not reached; the two- and three-year OS rates were 70% and 56%, respectively. The LSS was 80% at two years and 64% at three years. Conclusions: This Slovenian population-based study provides real-world insights into PVRL management. In elderly and medically fragile patients, local treatment modalities provided effective ocular disease control with acceptable toxicity.
Keywords: methotrexate, population-based study, primary vitreoretinal lymphoma, radiotherapy, survival analysis
Published in DiRROS: 24.04.2026; Views: 120; Downloads: 87
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2. Retinoblastoma with and without extraocular tumor extension : a global comparative study of 3435 patientsSwathi Kaliki, Vijitha S. Vempuluru, Ido Didi Fabian, 2025, original scientific article Abstract: Purpose
To study the treatment and outcomes of children with retinoblastoma (RB) with extraocular tumor extension (RB-EOE) and compare them with RB without extraocular tumor extension (RB-w/o-EOE).
Design
Multicenter intercontinental collaborative prospective study from 2017 to 2020. RB-EOE cases included those with overt orbital tumor extension in treatment-naive patients. Cases with microscopic orbital extension detected postenucleation were excluded from the study.
Participants
A total of 319 children with RB-EOE and 3116 children with RB-w/o-EOE.
Intervention
Chemotherapy, enucleation, exenteration, radiotherapy.
Main Outcome Measures
Systemic metastasis and death.
Results
Of the 3435 RB patients included in this study, 309 (9%) were from low-income countries (LIC), 1448 (42%) from lower-middle income, 1012 (29%) from upper-middle income, and 666 (19%) patients from high-income countries. There was an inverse relationship between the percentage of RB-EOE and national income level, with 96 (31%) patients from LIC, 197 (6%) lower-middle income, 20 (2%) upper-middle income, and 6 (1%) patients from high-income countries (P = 0.0001). The outcomes were statistically significant for RB-EOE compared with RB-w/o-EOE: systemic metastasis (32% vs. 4% respectively; P = 0.0001) and metastasis-related death (63% vs. 6% respectively; P = 0.0001). Multimodal treatment was the most common form of treatment (n = 177; 54%) for RB-EOE, with most cases undergoing a combination of intravenous chemotherapy and enucleation (n = 97; 30%). Adjuvant external beam radiotherapy (EBRT) after surgery (enucleation/orbital exenteration) was given in only 68 (21%) cases. Kaplan–Meier analysis for systemic metastasis and metastasis-related death in RB-EOE was 28% and 57% at 1 year, 29% and 60% at 2 years, and 29% and 61% at 3 years, respectively. Cox regression analysis revealed that the risk of death from RB-EOE was greater in patients aged >4 years than <2 years (hazard ratio, 2.912; P < 0.001) and for unimodal (surgery or intravenous chemotherapy) and bimodal (surgery and intravenous chemotherapy) treatment than trimodal treatment (surgery, intravenous chemotherapy, and EBRT) (hazard ratio, 2.023; P = 0.004 and hazard ratio, 1.819; P = 0.027, respectively).
Conclusions
Retinoblastoma with extraocular tumor extension is associated with a higher risk of metastasis and death. Patients with RB-EOE are likely to benefit from trimodal treatment (intravenous chemotherapy, surgery, and EBRT) rather than treatment protocols excluding EBRT.
Keywords: external beam radiotherapy, extraocular extension, multimodal treatment, retinoblastoma, tumor
Published in DiRROS: 10.03.2026; Views: 249; Downloads: 146
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3. Chemokine CCL5 overexpression combined with radiotherapy modulates Th1-mediated immune response and leads to significant tumor growth delay in mouse tumor modelsTim Božič, Iva Šantek, Živa Pišljar, Simona Kranjc Brezar, Gregor Serša, Boštjan Markelc, Maja Čemažar, 2026, original scientific article Abstract: This study investigated the antitumor efficacy of chemokine CCL5 gene therapy using gene electrotransfer (GET) in combination with radiotherapy (RT) in solid murine tumors CT26 and 4T1. In vitro, CT26 and 4T1 tumor cells transfected with plasmid DNA (pDNA) encoding CCL5 induced migration of RAW264.7 macrophages. In vivo, CCL5 overexpression achieved via GET of pDNA encoding CCL5 led to increased splenocyte infiltration in dorsal window chamber models. When combined with RT, GET of pDNA encoding CCL5 shifted the tumor cytokine profile toward a proinflammatory state, with elevated Ifn-γ, Cxcl9, Cxcl10, and Il-12α. Although CD8 + and CD4 + T cells were reduced post-treatment, due to radiation-induced cell death, the combination of GET of pDNA encoding CCL5 and RT significantly delayed tumor growth in both models. In 4T1 tumors, this delay was also significant compared to the equivalent treatment with GET of control pDNA. These findings support GET of pDNA encoding CCL5 combined with RT as a strategy to enhance immune-mediated tumor control.
Keywords: chemokines, gene electrotransfer, gene therapy, mouse, radiotherapy
Published in DiRROS: 13.02.2026; Views: 483; Downloads: 131
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4. Local control and survival after stereotactic body radiation therapy of early-stage lung cancer patients in SloveniaKarmen Stanič, Jasna But-Hadžić, Jan Žagar, Martina Vrankar, 2023, original scientific article Abstract: Background. Stereotactic body radiation therapy (SBRT) precisely and non-invasively delivers ablative radiationdose to tumors in early-stage lung cancer patients who are not candidates for surgery or refuse it. The aim of researchwas to evaluate local control, overall survival (OS), local progression free survival (LPFS), distant metastases free survival(DMFS), disease free survival (DFS) and toxicity in early-stage lung cancer patients treated with SBRT in a single tertiarycancer centre.Patients and methods. We retrospectively evaluated medical records and radiation treatment plan parametersof 228 tumors irradiated in 206 early-stage lung cancer patients between 2016 and 2021 at the Institute of OncologyLjubljana.Results. After 25 months of median follow up, 68 of 206 (33%) patients died. Median OS was 46 months (CI 36 −56),1-year, 2-year and 3-year OS were 87%, 74% and 62% and 5-year OS was 31%. A total of 45 disease progressions havebeen identified in 41 patients. Local progress only was noticed in 5 (2%) patients, systemic progress in 32 (16%) andcombined systemic and local in 4 (2%) patients. Local control rate (LCR) at 1 year was 98%, at 2 and 3 years 96%and 95% at 5 years. The 1-, 2- and 3-year LPFS were 98%, 96% and 94%, respectively and 5-year LPFS was 82%. One,2-, 3- and 5-year DFS w ere 89%, 81%, 72% and 49%, respectively. Among 28 toxicities recorded only one was Grade4 (pneumonitis), all others were Grade 1 or 2. No differences in LCR, LPFS, DFS were found in univariate analysis com-paring patient, tumor, and treatment characteristics. For OS the only statistically significant difference was found inpatients with more than 3 comorbidities compared to those with less comorbidities.Conclusions. Early lung cancer treated with SBRT at single tertiary cancer centre showed that LCR, LPFS, DFS, DMFSand OS were comparable to published studies. Patients with many comorbidities had significantly worse overallsurvival compared to those with less comorbidities. No other significant differences by patient, tumor, or treatmentcharacteristics were found for DMFS, LPFS, and DFS. Toxicity data confirmed that treatment was well tolerated.
Keywords: stereotactic body radiotherapy, early-stage lung cancer, lung cancer
Published in DiRROS: 25.07.2024; Views: 1255; Downloads: 743
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7. Simvastatin is effective in killing the radioresistant breast carcinoma cellsBertram Aschenbrenner, Giulia Negro, Dragana Savic, Maxim Sorokin, Anton A. Buzdin, Ute Maria Ganswindt, Maja Čemažar, Gregor Serša, Sergej Skvortsov, Ira Skvortsova, 2021, original scientific article Abstract: Background. Statins, small molecular 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are widely used to lower cholesterol levels in lipid-metabolism disorders. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer by increasing recurrence free survival. Unfortunately, the underlying mechanisms remain elusive. Materials and methods. Simvastatin, one of the most widely prescribed lipophilic statins was utilized to investigate potential radiosensitizing effects and an impact on cell survival and migration in radioresistant breast cancer cell lines. Results. Compared to parental cell counterparts, radioresistant MDA-MB-231-RR, T47D-RR andAu565-RR cells were characterized by upregulation of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMGCR) expression accom-panied by epithelial-to-mesenchymal transition (EMT) activation. Radioresistant breast cancer cells can be killed by simvastatin via mobilizing of a variety of pathways involved in apoptosis and autophagy. In the presence of simvasta-tin migratory abilities and vimentin expression is diminished while E-cadherin expression is increased. Conclusions. The present study suggests that simvastatin may effectively eradicate radioresistant breast carcinoma cells and diminish their mesenchymal phenotypes.
Keywords: radiotherapy, breast cancer, radioresistant cells
Published in DiRROS: 22.07.2024; Views: 1325; Downloads: 796
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8. Hyperthermia as a potential cornerstone of effective multimodality treatment with radiotherapy, cisplatin and PARP inhibitor in IDH1-mutated cancer cellsMohammed Khurshed, Elia Prades-Sagarra, Sarah Al Saleh, Peter Sminia, Johanna W Wilmink, Remco J. Molenaar, Hans Crezee, Cornelis J. F. van Noorden, 2022, original scientific article Abstract: Mutations in the isocitrate dehydrogenase 1 (IDH1MUT) gene occur in various types of malignancies, including ~60% of chondrosarcomas, ~30% of intrahepatic cholangiocarcinomas and >80% of low-grade gliomas. IDH1MUT are causal in the development and progression of these types of cancer due to neomorphic production of the oncometabolite D-2-hydroxyglutarate (D-2HG). Intracellular accumulation of D-2HG has been implicated in suppressing homologous recombination and renders IDH1MUT cancer cells sensitive to DNA-repair-inhibiting agents, such as poly-(adenosine 5′-diphosphate–ribose) polymerase inhibitors (PARPi). Hyperthermia increases the efficacy of DNA-damaging therapies such as radiotherapy and platinum-based chemotherapy, mainly by inhibition of DNA repair. In the current study, we investigated the additional effects of hyperthermia (42 °C for 1 h) in the treatment of IDH1MUT HCT116 colon cancer cells and hyperthermia1080 chondrosarcoma cancer cells in combination with radiation, cisplatin and/or a PARPi on clonogenic cell survival, cell cycle distribution and the induction and repair of DNA double-strand breaks. We found that hyperthermia in combination with radiation or cisplatin induces an increase in double-strand breaks and cell death, up to 10-fold in IDH1MUT cancer cells compared to IDH1 wild-type cells. This vulnerability was abolished by the IDH1MUT inhibitor AGI-5198 and was further increased by the PARPi. In conclusion, our study shows that IDH1MUT cancer cells are sensitized to hyperthermia in combination with irradiation or cisplatin and a PARPi. Therefore, hyperthermia may be an efficacious sensitizer to cytotoxic therapies in tumors where the clinical application of hyperthermia is feasible, such as IDH1MUT chondrosarcoma of the extremities.
Keywords: isocitrate dehydrogenase, PARP, hyperthermia, D‐2‐hydroxyglutarate, radiotherapy, cisplatin
Published in DiRROS: 18.07.2024; Views: 1283; Downloads: 923
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9. Breast size and dose to cardiac substructures in adjuvant three-dimensional conformal radiotherapy compared to tangential intensity modulated radiotherapyIvica Ratoša, Aljaša Jenko, Željko Šljivić, Maja Pirnat, Irena Oblak, 2020, original scientific article Abstract: The aim of the study was to quantify planned doses to the heart and specific cardiac substructures in free-breathing adjuvant three-dimensional radiation therapy (3D-CRT) and tangential intensity modulated radiotherapy (t-IMRT) for left-sided node-negative breast cancer, and to assess the differences in planned doses to organs at risk according to patients% individual anatomy, including breast volume. Patients and methods. In the study, the whole heart and cardiac substructures were delineated for 60 patients using cardiac atlas. For each patient, 3D-CRT and t-IMRT plans were generated. The prescribed dose was 42.72 Gy in 16 fractions. Patients were divided into groups with small, medium, and large clinical target volume (CTV). Calculated dose distributions were compared amongst the two techniques and the three different groups of CTV. Results. Mean absorbed dose to the whole heart (MWHD) (1.9 vs. 2.1 Gy, P < 0.005), left anterior descending coronary artery mean dose (8.2 vs. 8.4 Gy, P < 0.005) and left ventricle (LV) mean dose (3.0 vs. 3.2, P < 0.005) were all significantly lower with 3D-CRT technique compared to t-IMRT. Apical (8.5 vs. 9.0, P < 0.005) and anterior LV walls (5.0 vs. 5.4 Gy, P < 0.005) received the highest mean dose (Dmean). MWHD and LV-Dmean increased with increasing CTV size regardless of the technique. Low MWHD values (< 2.5 Gy) were achieved in 44 (73.3%) and 41 (68.3%) patients for 3D-CRT and t-IMRT techniques, correspondingly. Conclusions. Our study confirms a considerable range of the planned doses within the heart for adjuvant 3D-CRT or t-IMRT in node-negative breast cancer. We observed differences in heart dosimetric metrics between the three groups of CTV size, regardless of the radiotherapy planning technique.
Keywords: breast cancer, radiotherapy, 3D-CRT
Published in DiRROS: 16.07.2024; Views: 1114; Downloads: 473
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10. Combining radiotherapy and immunotherapy in definitive treatment of head and neck squamous cell carcinoma : review of current clinical trialsGaber Plavc, Primož Strojan, 2020, review article Abstract: Head and neck squamous cell carcinoma (HNSCC) presents as locally advanced disease in a majority of patients and is prone to relapse despite aggressive treatment. Since immune checkpoint inhibitors (ICI) have shown clinically significant efficacy in patients with recurrent/metastatic HNSCC (R/M HNSCC), a plethora of trials are investigating their role in earlier stages of disease. At the same time, preclinical data showed the synergistic role of concurrently administered radiotherapy and ICIs (immunoradiotherapy) and explained several mechanisms behind it. Therefore, this approach is prospectively tested in a neoadjuvant, definitive, or adjuvant setting in non-R/M HNSCC patients. Due to the intricate relationship between host, immunotherapy, chemotherapy, and radiotherapy, each of these approaches has its advantages and disadvantages. In this narrative review we present the biological background of immunoradiotherapy, as well as a rationale for, and possible flaws of, each treatment approach, and provide readers with a critical summary of completed and ongoing trials. Conclusions. While immunotherapy with ICIs has already become a standard part of treatment in patients with R/M HNSCC, its efficacy in a non-R/M HNSCC setting is still the subject of extensive clinical testing. Irradiation can overcome some of the cancer%s immune evasive manoeuvres and can lead to a synergistic effect with ICIs, with possible additional benefits of concurrent platinum-based chemotherapy. However, the efficacy of this combination is not robust and details in trial design and treatment delivery seem to be of unprecedented importance.
Keywords: head and neck neoplasms, immunoradiotherapy, radiotherapy, immunotherapy
Published in DiRROS: 16.07.2024; Views: 1174; Downloads: 368
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