Ewing sarcoma (ES) is the second most common primary bone malignancy after osteosarcoma. The disease most often occurs in adolescence, with peak incidence around the age of fourteen. The most common primary location of the tumor is the bones of the pelvis, followed by the ribs, spine and long bones of the extremities such as the tibia and the fibula. ES shows a tendency towards hematogenous dissemination, primarily in the lungs and bones, much less often lymphogenously. One third of patients have distant metastases present at initial diagnosis, which is why ES is considered a systemic disease. The treatment of Ewing sarcoma is based on a multimodal approach that includes the use of chemotherapy, surgery and/or radiotherapy. The identification of prognostic parameters enabled the individual treatment of patients based on the assessed risk group. With the application of modern therapeutic protocols, five-year survival for patients with localized disease lies between 60% and 68%, while for patients with metastatic disease, five-year survival is still unsatisfactory and is around 17%. ES belongs to the group of radiosensitive tumors, and radiotherapy plays a very important role in the local control of the disease, in combination with surgical treatment or independently, and can be applied as radical, preoperative or postoperative radiation therapy. Also, radiation therapy has a role in the palliative approach to the treatment of lung metastases and other metastatic sites. Considering that the modern multimodal treatment of Ewing sarcoma leads to long-term survival, it is necessary to take into account the expected side effects of the therapy that can reduce the quality of life of treated patients. Modern radiotherapy techniques such as three-dimensional conformal radiation therapy (3D CRT), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) enable precise delivery of the prescribed dose of radiation to target volumes with better sparing of surrounding normal tissues and organs, which leads to a lower incidence of late sequelae of radiation therapy and enables the preservation of the quality of life of treated patients.

Proton beam therapy (PBT) is an advanced type of radiotherapy that shows a dosimetric advantage over photon beam therapy and provides superior dose distribution. PBT may improve patient survival by improving the local disease control while reducing toxicity to normal organs, which may result in fewer treatment related complications. During the last decade technological progress opened up new possibilities in the planning and conducting PBT, so indications were gradually expanded to different cancers. However, many biological aspects of PBT are still unclear, and its role in clinical settings is controversial. Proton therapy is considered to be safe and effective for different types of pediatric cancers, and that it is suitable in treatment of ocular melanomas, chordomas and chondrosarcomas. Future research and more prospective clinical studies with long term follow up are required in order to clearly determine the benefits and proper indications for PBT.

Rhabdomyosarcoma is the most common soft tissue sarcoma among children and represents half of all soft tissue sarcomas. The tumor is derived from primitive mesenchymal stem cells which develop into striated muscle and common sites of occurrence are the head and neck region, genitourinary tract and extremities. Treatment is multimodal and includes surgery, radiotherapy and chemotherapy. Application of combined treatment led to significant improvement in treatment outcome. Due to long-term survival, great importance is given to the expected treatment complications. Therapy for pediatric rhabdomyosarcoma requires a delicate balance between the need to intensify therapy for certain group of patients and the desire to reduce potentially toxic therapy and risk for secondary malignancies for patients with good prognosis. Radiotherapy plays an important role in local control of disease and is performed in nearly all patients. Since it is applied to organs and tissues that are in growth and development phase, radiotherapy in childhood has its own specificity and represents greater challenge in relation to the treatment of adult patients. The use of modern radiotherapy techniques ensures excellent local control of disease with better sparing of normal surrounding tissues which reduces radiotherapy toxicity and preserves quality of life of treated children.

Introduction: Patients with locally advanced cervical cancer (LACC) are commonly treated with definitive chemoradiotherapy (CRT), consisting of external beam radiotherapy (EBRT), concurrent chemotherapy, and brachytherapy. Advances in radiotherapy techniques and imaging over the past decade have led to important changes in treatment delivery. This study aimed to evaluate temporal changes in CRT delivery in patients with LACC. Methods: This retrospective single-center cohort study included 200 patients with LACC treated with definitive CRT at the Institute for Oncology and Radiology of Serbia. Two cohorts were analyzed: 100 patients treated in 2010-2011 and 100 patients treated in 2022-2023. Clinical and treatment-related parameters, including chemotherapy administration, EBRT technique, dose and fractionation, brachytherapy characteristics, and baseline patient characteristics, were compared. Results: Significant differences were observed between the two cohorts. The use of concurrent chemotherapy and the number of administered cycles differed significantly between the two cohorts (p < 0.001). A complete transition from conventional radiotherapy techniques to IMRT/VMAT was observed in the later period (p < 0.001), along with the introduction of simultaneous integrated boost (SIB). Differences were also identified in EBRT fractionation and total dose (p < 0.001). In brachytherapy, significant variations in dose and fractionation were observed (p < 0.001 and p < 0.05), while applicator type remained comparable. Conclusion: Significant temporal changes in CRT delivery were observed, reflecting the adoption of modern radiotherapy techniques and evolving treatment strategies. These findings indicate increasing treatment individualization and greater use of contemporary radiotherapy approaches in routine clinical practice within a middle-income setting.

Background: Glioblastoma is the most lethal primary brain tumor, being characterized not only by marked intratumoral heterogeneity but also by strong systemic immunosuppression. Circulating extracellular vesicles (EVs) have gained growing recognition during the past decade as important mediators of intercellular communication, particularly through their microRNA (miRNA) cargo. However, the global EV miRNA landscape of circulating EV-associated miRNAs in glioblastoma patients and their relation with gene expression patterns in peripheral immune cells remain incompletely defined. Methods: To investigate these systemic associations, we profiled EV-associated miRNA expression in plasma samples from glioblastoma patients and matched healthy controls using the small RNA sequencing method, followed by differential expression and pathway analyses. Based on these findings and literature evidence, identified changes in selected EV miRNA levels were validated by qPCR in an extended cohort. In parallel, expression of their predicted immune-related mRNA targets was analyzed in peripheral blood mononuclear cells (PBMCs) obtained from the same individuals, allowing for the assessment of EV miRNA–PBMC mRNA correlation patterns. Results: Small RNA sequencing revealed a distinct circulating EV-associated miRNA profile in glioblastoma patients compared to controls. The validation analysis of relative expression of the identified DEmiRNAs has shown a statistically significant upregulation of hsa-miR-142-3p, hsa-miR-19b-3p, and hsa-miR-98-5p in circulating EVs of glioblastoma patients compared to controls. PBMCs from glioblastoma patients exhibited increased expression of the regulatory genes SOCS1, SOCS3, and PTEN, while CCND1 was downregulated. Correlation analyses suggested that certain EV miRNA changes parallel with alterations in PBMC gene expression in glioblastoma patients, suggesting early immune priming in the circulation. Conclusions: Our findings indicate that circulating EV miRNAs in glioblastoma patients are associated with specific gene expression patterns in peripheral immune cells, suggesting a complex regulatory balance between pro-inflammatory and anti-inflammatory cues, potentially preceding full tumor-associated macrophage polarization. These molecular interactions may offer opportunities for developing early biomarkers or new therapeutic approaches.

Background: Organized cervical cancer screening aims to reduce the burden of advanced disease through earlier detection. However, a substantial proportion of women continue to present with locally advanced cervical cancer (LACC) requiring definitive chemoradiation. This study evaluated temporal changes in the demographic and clinicopathological characteristics of women with LACC treated with definitive chemoradiation before and after implementation of the organized cervical cancer screening program in Serbia. Methods: This retrospective single-center cohort study included 200 consecutive women with histologically confirmed LACC treated with definitive chemoradiation at the Institute of Oncology and Radiology of Serbia. Two cohorts were analyzed: a pre-screening cohort (2010–2011, n = 100) and a post-screening cohort (2022–2023, n = 100). Demographic and clinicopathological characteristics, including age, histopathology, FIGO stage, lymph node involvement, and geographic distribution, were compared. For study purposes, all patients were retrospectively restaged according to the FIGO 2018 classification using the best available clinical, radiological, and pathological data. Results: Women in the post-screening cohort were significantly older at diagnosis than those in the pre-screening cohort (mean age 54.9 vs. 49.7 years, p = 0.0046), with a substantially higher proportion of patients older than 64 years (28% vs. 2%, p < 0.0001). Although the overall distribution of FIGO stages II–IV did not differ significantly, a marked redistribution of FIGO 2018 substages was observed (p < 0.0001), characterized by an increased proportion of stage IIIC disease and significantly more frequent lymph node involvement (63% vs. 41%, p = 0.0018). Geographic distribution remained stable, with most patients referred from the Belgrade administrative district. Conclusions: This study demonstrated clinically relevant temporal changes in the demographic and clinicopathological characteristics of women requiring definitive chemoradiation for LACC in Serbia. More than a decade after implementation of organized cervical cancer screening, tertiary referral centers continue to manage a substantial burden of patients with locally advanced disease requiring complex, resource-intensive treatment. These findings should not be interpreted as a direct evaluation of the national screening program but may provide valuable insights for healthcare planning in Serbia and other countries with similarly resource-constrained healthcare systems. Strengthening participation in organized screening, ensuring timely diagnostic evaluation, and improving HPV vaccination uptake remain essential to reduce the burden of advanced cervical cancer.