Radiation, Volume 6, Issue 3 (September 2026) – 14 articles

Pancreatic neuroendocrine neoplasms (PanNENs) are a heterogeneous group of tumors characterized by variable biological behavior and frequent overexpression of somatostatin receptors, making them ideal candidates for theranostic approaches. Over the past two decades, advances in molecular imaging and peptide receptor radionuclide therapy (PRRT) have fundamentally transformed the diagnosis and management of advanced PanNENs, establishing nuclear medicine as a central component of precision oncology. This review provides a comprehensive overview of the evolving role of theranostics in PanNENs, with particular emphasis on recent developments in nuclear medicine and radiation-based precision medicine. We discuss the biological foundation of molecular imaging, current clinical evidence supporting PRRT, and emerging strategies for personalized radionuclide therapy based on quantitative imaging, patient selection, and individualized dosimetry. Furthermore, we highlight next-generation radiopharmaceuticals, including somatostatin receptor antagonists and α-emitting radionuclides, as well as novel diagnostic tracers that are expanding the scope of theranostic applications. The review also examines the growing impact of artificial intelligence, radiomics, and computational modeling in image analysis, treatment planning, and adaptive radionuclide therapy. Finally, we discuss future perspectives toward adaptive precision theranostics, in which molecular imaging, multi-omics integration, advanced dosimetry, and artificial intelligence converge to support dynamic, patient-specific treatment strategies. Continued technological innovation and multidisciplinary collaboration are expected to further establish theranostics as a cornerstone of personalized management for patients with PanNENs. Full article

Background: Radiotherapy commonly requires a computed tomography (CT) dataset for treatment planning. Artificial intelligence-supported radiotherapy systems now enable online adaptive workflows that reduce uncertainties resulting from the use of diagnostic instead of planning CT images. The aim was to identify patient groups that may particularly benefit from adaptive emergency treatments. Methods: In this retrospective exploratory study, 16 patients comprising 21 planning target volumes (PTVs) were evaluated. PTVs were classified as predominantly soft-tissue or bony. To verify the geometric agreement between scheduled and adapted treatment plans, these subgroups were analyzed using absolute planning target volume change, the Dice similarity coefficient (DSC), and the 95th percentile Hausdorff distance, and their association with V95% PTV coverage was evaluated. Results: Bony targets showed higher geometric reproducibility than soft-tissue-dominant lesions, with higher median DSC values (0.96 vs. 0.88) and lower median HD95 values (2.6 mm vs. 5.5 mm). Online adaptation improved coverage in 20 of 21 PTVs, while predominantly soft-tissue PTVs showed potentially greater benefit from online adaptation. Conclusions: Soft-tissue-dominant PTVs showed greater geometric variability and potentially greater benefit from adaptation, whereas selected bone-dominant cases may be suitable for faster conventional workflows. Given the small exploratory cohort, these results require further confirmation. Full article

Introduction: The increasing costs of cancer care have raised the need for economic evaluations that integrate treatment efficacy and resource utilization. This study aimed to assess the economic value of Lutetium-177 (¹⁷⁷Lu)–prostate-specific membrane antigen (PSMA)-617 in patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) from an Italian healthcare perspective. Patients and Methods: A cost-effectiveness analysis was performed using clinical efficacy data from randomized controlled trials (RCTs) evaluating ¹⁷⁷Lu-PSMA-617. Two scenarios were considered. Scenario 1 evaluated ¹⁷⁷Lu-PSMA-617 plus standard care (SC) versus SC alone using pivotal phase III trial data. Scenario 2 compared ¹⁷⁷Lu-PSMA-617 with chemotherapy and androgen receptor pathway inhibitors (ARPIs) using phase II and III RCTs. Drug costs were based on Italian ex-factory prices. In addition, an exploratory three-state Markov cost–utility model including progression-free survival (PFS), progressive disease, and death was developed using data from the VISION trial. Results: In Scenario 1, 730 patients were analyzed. The ESMO-MCBS grade was 3, and the incremental cost per month of PFS gained with ¹⁷⁷Lu-PSMA-617 versus SC was €20,906. In Scenario 2, 651 patients were included. The monthly cost per PFS gained with ¹⁷⁷Lu-PSMA-617 was €19,017 versus enzalutamide and €20,565 versus abiraterone. In the exploratory cost–utility model, estimated QALYs were 1.02 with ¹⁷⁷Lu-PSMA-617 and 0.64 with SC, corresponding to an incremental gain of 0.38 QALYs. At an incremental cost of approximately €32,000 per patient, the resulting model-based ICER was approximately €85,000/QALY. Conclusions:¹⁷⁷Lu-PSMA-617 provides meaningful clinical benefit in appropriately selected patients with PSMA-positive mCRPC, but this benefit is associated with substantial incremental treatment costs. The exploratory model-based ICER was sensitive to treatment duration and other model assumptions. These findings support careful assessment of the clinical value and economic sustainability of ¹⁷⁷Lu-PSMA-617 in the Italian healthcare setting. Further studies incorporating real-world resource utilization, treatment-related costs, post-progression therapies, and prospectively collected quality-of-life data are warranted. Full article

This study aimed to evaluate the utility of a 3D-printed, weight-bearing auxiliary device designed to improve reproducibility and facilitate detector fixation during axiolateral radiography of hip joints known to be affected by inter-operator variability. The experiment was conducted using a radiolucent human phantom. Multiple radiographs were taken under identical conditions. Reproducibility and utility were assessed by measuring the α angle and off-set ratio from acquired images. Results showed that the mean α angle was 51.58° (±5.14°) with the auxiliary device and 50.45° (±4.90°) without it, with no statistically significant difference between conditions (Wilcoxon signed-rank test, p = 0.2024), indicating no measurable improvement in reproducibility. The off-set ratio likewise did not differ significantly between conditions (p = 0.1704). However, using the device did not significantly affect the off-set ratio. In conclusion, the auxiliary device developed in this study allows for consistent detector angle maintenance and fixation during hip joint axiolateral projection, thereby improving reproducibility and ease of examination. This suggests its potential usefulness for achieving more accurate imaging in clinical settings. Full article

Symptomatic high-grade carotid stenosis may present with extensive ipsilateral hemispheric hypoperfusion without a large infarct core, a grey-zone phenotype between standard early and truly urgent carotid revascularization. This single-centre retrospective observational study described the procedural and clinical outcomes of urgent carotid revascularization in this imaging-defined subgroup. Consecutive patients treated between June 2015 and August 2025 were included when they had recent ipsilateral anterior-circulation symptoms, ipsilateral internal carotid stenosis > 70%, objective hemispheric hypoperfusion involving at least one third of the anterior circulation territory on CT or MR perfusion, and no intracranial haemorrhage or large established infarction. Twenty-seven patients met the criteria. Median NASCET-style stenosis was 92%, and 14 patients (51.9%) had at least one collateral-limiting feature. Revascularization was performed within 48 h in all cases, by carotid endarterectomy in 25 patients and carotid artery stenting in two. Technical success was 100%. No 30-day death, stroke, intracranial haemorrhage, major adverse event, or target-lesion reintervention occurred. Complete neurological recovery at discharge was observed in 25 patients (92.6%). During median follow-up of 48.6 months, no late ipsilateral stroke, carotid-related neurological event, neurological death, or target-lesion reintervention was recorded. In this small, selected, uncontrolled cohort, urgent carotid revascularization was technically achievable, and no prespecified 30-day safety events were observed. These descriptive findings do not establish comparative safety or clinical benefit and require prospective multicentre validation. Full article

Endovascular aneurysm repair (EVAR) has become a widely adopted treatment for abdominal aortic aneurysms, offering lower perioperative morbidity and mortality than open surgical repair. Nevertheless, long-term imaging surveillance remains essential because procedure-related complications may occur years after treatment. Among these, endoleaks represent the most frequent and clinically relevant finding, particularly Type II endoleaks, which are sustained by retrograde collateral perfusion and may be associated with persistent aneurysm sac filling and sac enlargement. Computed tomography angiography (CTA) remains the reference standard for anatomical assessment after EVAR, providing detailed evaluation of endograft integrity, aneurysm sac morphology, and vascular anatomy. However, repeated CTA examinations involve cumulative radiation exposure and iodinated contrast administration and may be limited in the detection of low-flow or intermittent endoleaks. Contrast-enhanced ultrasound (CEUS) provides real-time hemodynamic assessment, improves detection of slow-flow endoleaks, and avoids both ionizing radiation and nephrotoxic contrast agents. Nevertheless, CEUS may be affected by operator dependency and limited anatomical overview. CT–ultrasound fusion imaging combines pre-acquired CTA datasets with real-time ultrasound through spatial co-registration and probe tracking, enabling simultaneous evaluation of vascular anatomy and flow dynamics. This narrative review critically synthesizes current evidence regarding CTA, CEUS, and CT–ultrasound fusion imaging in post-EVAR surveillance, with particular emphasis on the incremental clinical value of fusion imaging beyond standalone CTA and CEUS. Particular attention is devoted to diagnostic performance, technical implementation, clinical applicability, current limitations, and future perspectives of CT–CEUS fusion imaging. Full article

Background: High-dose-rate interventional radiotherapy (HDR IRT) relies on accurate dose calculations to ensure safe and effective treatment. The AAPM TG-43 formalism, based on homogeneous water assumptions, has long been the clinical standard, but the growing use of patient-specific applicators and heterogeneous materials challenges its accuracy. Materials and Methods: A literature narrative review was performed using PubMed and Scopus to identify studies comparing TG-43 and model-based dose calculation algorithms (MBDCAs), including deterministic methods (ACE, Acuros BV) and Monte Carlo simulations. Thirty-five studies were selected and qualitatively analyzed. Results: TG-43 yielded higher dose compared with MBDCAs, particularly in the presence of tissue heterogeneities, air gaps, shielding materials, and limited scatter conditions. Differences ranged from 2 to 5% in relatively homogeneous settings to more than 10–20% in complex geometries such as superficial mould treatments and head-and-neck IRT. Model-based approaches showed better agreement with Monte Carlo simulations and experimental measurements, especially in contact HDR IRT and applications involving 3D-printed applicators. Conclusion: While TG-43 remains clinically established and widely used, its limitations are increasingly evident in modern personalized HDR IRT. Model-based dose calculation algorithms provide greater dosimetric accuracy and should be progressively integrated into clinical practice, particularly in treatments involving significant heterogeneities. Full article

The aim of this study was to compare the accuracy of different sub-200 µm voxel reconstruction of CBCT scans in the identification of root canal anatomy. Cadaveric dentate maxillae and mandibles with soft tissues attached (69 teeth comprising 91 roots) were assessed with scans reconstructed at voxel sizes of 80 µm, 125 µm, and 160 µm. Three examiners recorded the canal configuration, presence of lateral canals, PAI score, and image quality seen on the scans. Micro-computed tomography (micro-CT) scans of the specimens reconstructed at 10 µm served as the reference standard. There was no significant difference between 80 µm and 125 µm reconstructions, but 80 µm scans were more accurate than 160 µm scans (p = 0.04). The findings suggest that canal anatomical complexity may have a greater influence on diagnostic accuracy than differences among the sub-200 µm voxel reconstructions evaluated. Lateral canals were only noted in 2% of roots in CBCT scans, but were present in 55% of roots assessed with micro-CT. There was significantly more variation in the assessment of image quality for 80 µm compared with 125 µm (p = 0.01) and 160 µm (p = 0.003) scans. Generally, 80 µm reconstructions provided marginally improved diagnostic yield compared with 160 µm scans; however, CBCT scans showed limited accuracy for more complex canal configurations. The poorer image quality of 80 µm scans may be due to the limited field of view, which causes partial volume effects rather than being reconstructed at 80 µm per se. Full article

Background: Actinium-225 (²²⁵Ac) is receiving major attention as the radionuclide of choice for targeted alpha therapy (TAT) due to its outstanding physical properties such as a long physical half-life of 9.9 days and a short range of alpha (α)-particles which are responsible for the destruction of malignant tumors, whilst sparing normal surrounding tissues. Although the physical properties of ²²⁵Ac make it a desirable radionuclide for TAT, its application is challenging due to the lack of chelators available to stabilize its daughter radionuclides, resulting in the recoil effect. This occurs when there is a breakdown between the radionuclide and the chelator, therefore minimizing the therapeutic effects of the radiopharmaceutical. Nanodrug delivery systems (NDDSs) may minimize the challenge of ²²⁵Ac’s recoiling daughters and increase tumor penetration. Aim: This study aimed at using poly(lactic-co-glycolic)acid (PLGA) and chitosan (CS) nanoparticles as a delivery vehicle for targeted alpha therapy of prostate cancer in order to increase the therapeutic effect of ²²⁵Ac PSMA617-TFA. Methods and Results: PLGA nanoparticles were prepared using a nanoprecipitation method, after which they were functionalized with chitosan and folic acid. Following synthesis of ²²⁵Ac PSMA617-TFA, the radiopharmaceutical was loaded onto the nanoparticles. SEM analysis and FTIR were performed for characterization of the nanoparticles, and in-vitro drug release of ²²⁵Ac PSMA617-TFA at pH = 6.5 and pH = 7.4, respectively, was measured. The nanoparticles prepared had an average size of 200 nm and had a positive charge. This was further confirmed using a zetasizer and with scanning electron microscope (SEM) analysis. The PLGA-CS nanoparticles indicated a high encapsulation efficiency after 24 h. The results also showed a controlled release of ²²⁵Ac PSMA617-TFA over 72 h. The results of this study indicate that PLGA-CS nanoparticles are suitable for retaining ²²⁵Ac and its recoiling daughters (²²¹Fr and ²¹³Bi) at the tumor site, potentially providing a platform for future therapeutic evaluation. Conclusions: The results of this study indicate that PLGA-CS nanoparticles demonstrate feasibility as a drug delivery vehicle for ²²⁵Ac PSMA617-TFA, with effective retention of ²²⁵Ac and its decay daughters. However, biological validation through in vitro cellular studies and in vivo preclinical models is required before therapeutic effectiveness can be established. Full article

Osteoradionecrosis of the jaw (ORNJ) remains one of the most severe late complications of head and neck radiotherapy. Current evidence suggests that ORNJ is a progressive and biologically heterogeneous disorder driven by microvascular injury, chronic hypoxia, oxidative stress, fibro-atrophic remodeling, impaired bone turnover, immune dysregulation, and systemic susceptibility factors. Within this complex pathogenic network, heat shock protein 27 (HSP27) emerges as a biologically plausible but unexplored mediator. HSP27 regulates multiple stress-response pathways, including redox homeostasis, cytoskeletal stabilization, endothelial protection, apoptosis control, fibroblast activation, and osteoblast–osteoclast function, all of which overlap with key mechanisms implicated in ORNJ. However, no studies have directly investigated HSP27 expression, activation, or functional significance in irradiated mandibular tissues or ORNJ-specific cohorts. This review summarizes current knowledge of ORNJ pathobiology, examines potential mechanistic links with HSP27, and outlines future research priorities involving biomarker development, tissue-level characterization, preclinical modeling, and therapeutic targeting. Integrating HSP27 into ORNJ research may improve understanding of pathogenesis, risk stratification, and the development of novel preventive and therapeutic strategies. Full article

Radiotherapy for glioblastoma remains anchored to postoperative structural MRI and anatomy-based target definitions, despite marked spatial heterogeneity and dynamic biological change during chemoradiotherapy. Advanced MRI, amino-acid PET, radiomics, and habitat imaging can characterize tumor biology beyond conventional anatomy, yet their relevance to radiotherapy planning and their evidentiary maturity differ substantially. This narrative review examines the current evidence for biologically informed radiotherapy in glioblastoma and proposes an imaging-based actionability framework that organizes imaging-derived findings into five levels of evidentiary maturity, from descriptive or associative signals to intervention-ready biomarkers, to guide literature interpretation, multidisciplinary discussion, and prospective protocol design. Standard MRI-based planning remains the clinical backbone, supported by contemporary guidelines and the absence of randomized evidence demonstrating benefit from routine biologically guided target modification. Advanced MRI is discussed as the most practical serial platform for treatment-course reassessment, amino-acid PET as a selective complementary tool for metabolic clarification and recurrence assessment, and radiomics and habitat imaging as promising but not yet intervention-ready research layers. Across modalities, prospective evidence supports feasibility more consistently than clinical benefit. The proposed framework is intended to separate biologically informative findings from those sufficiently validated to justify a defined radiotherapy consequence, and to structure the translational path toward intervention-grade evidence in glioblastoma radiotherapy. Full article

Accurate calculation of gamma dose rates in medical and industrial facilities is a critical component of comprehensive dosimetry assessment. Usually, two complementary approaches are employed to this end: experimental measurements and Monte Carlo (MC) simulations, both of which have established themselves as powerful and reliable tools in radiation protection and dosimetry practice. Given the high computational cost of Monte Carlo simulations, artificial intelligence can offer a compelling and efficient alternative for predicting dose rate distributions. This study evaluates the capability of machine learning models to predict MC-calculated dose rates and to identify the optimal ⁶⁰Co source arrangement for the upcoming replenishment. The replenishment scenario involves inserting six new ⁶⁰Co pencil sources. Dose rate prediction was performed using FLUKA MC simulations, complemented by an Artificial Neural Network (ANN)-based predictive model. The ANN model demonstrated strong concordance with FLUKA MC results, with deviations consistently below 1%, and exhibited reliable predictive performance on previously unseen configurations. Based on the dose uniformity ratio and the coefficient of determination, configuration 3 was identified as the optimal arrangement (R² = 0.986). The integration of machine learning with MC simulation proves highly effective, enabling rapid and accurate dose rate prediction around the ⁶⁰Co source while substantially reducing computational time and CPU resource demands. Full article

Radiation therapy is central to the management of gynecological cancers, including endometrial, cervical, ovarian, and vaginal malignancies. Despite advances in photon-based techniques, treatment-related toxicity remains significant owing to the anatomical proximity of pelvic targets to critical organs at risk (OARs), including the bowel, bladder, and bone marrow. Proton beam therapy exploits the Bragg peak to deliver a precise dose at depth with minimal exit dose, potentially reducing OAR exposure. This review develops the physical principles, dosimetric evidence, and early clinical data for proton therapy in gynecological malignancies, including cervical, endometrial, ovarian, vaginal, and vulvar cancers. Major focus is given to clinical conditions where conventional brachytherapy is not practical, and proton therapy may offer the greatest advantages, such as reirradiation for recurrent disease, post-operative pelvic irradiation, and extended field nodal treatment. This review also emphasizes current constraints that have slowed down wide clinical implementation, such as the lack of mature prospective data, cost, and accessibility. Finally, we emphasize future directions, including well-designed comparative trials, integration with systemic and immunotherapies, and adaptive treatment strategies. As the body of accumulated evidence evolves, the proton beam therapy potential for the treatment of gynecological malignancies has tremendously increased due to its role in safety and personalization of radiation treatment. Full article

Background: Pancreatic resection (Pancreatoduodenectomy, PD, distal pancreatectomy, DP, or total pancreatectomy, TP) is the standard of care for resectable pancreatic adenocarcinoma (PDAC). Despite advances in multimodal therapy, recurrence rates remain high, approaching 80%, and continue to drive poor overall survival. Objective: This review evaluates the burden and clinical significance of localized recurrence in PDAC and critically examines the potential role of intraoperative radiation therapy (IORT) in improving locoregional disease control. Results: Distant recurrence remains the predominant pattern of failure, occurring in 55–75% of patients, most commonly involving the liver, lungs, and peritoneum. However, isolated local recurrence, observed in approximately 17–32% of patients, represents a clinically meaningful subset associated with significant morbidity and potential for subsequent metastatic progression. IORT, delivered as a single high-dose radiation treatment to the tumor bed at the time of surgery, enables precise targeting of areas at highest risk for residual microscopic disease while minimizing radiation exposure to adjacent radiosensitive structures. Retrospective and meta-analytic data, while limited, suggest that IORT is associated with improved local control and modest survival benefit without a significant increase in perioperative morbidity, though interpretation is limited by study heterogeneity and lack of randomized control trials. Conclusion: IORT represents a rational adjunct in the multimodal management of PDAC, particularly for patients at high risk of locoregional failure, including those with borderline resectable or locally advanced disease, nodal involvement, perineural invasion, or concern for margin positivity. Prospective studies are needed to better define optimal patient selection and to clarify the role of IORT in the modern treatment paradigm. Full article