Radiation, Volume 5, Issue 4 (December 2025) – 13 articles

Radiopharmaceutical therapy (RPT) offers tumor-selective radiation delivery and represents a promising platform for combination with immune checkpoint inhibitors (ICIs). While prior studies suggest that RPT can stimulate antitumor immunity, synergy with ICIs may depend on radionuclide properties, absorbed dose, and radiation distribution within the tumor microenvironment. This study evaluated how radionuclide selection and dose influence immune stimulation and therapeutic efficacy of GD2-targeted antibody-based RPT combined with ICIs. Dinutuximab, an anti-GD2 monoclonal antibody, was radiolabeled with β⁻-emitters (⁹⁰Y, ¹⁷⁷Lu) or an α-emitter (²²⁵Ac). C57Bl6 mice bearing GD2⁺ tumors received 4 or 15 Gy tumor-absorbed doses, determined by individualized dosimetry, with or without dual ICIs (anti-CTLA-4 and anti-PD-L1). In vivo imaging, ex vivo biodistribution, survival, histological, and gene expression analyses were performed to assess therapeutic and immunological outcomes. All radiolabeled constructs demonstrated preferential uptake in GD2⁺ tumors. Combination therapy improved survival in a radionuclide- and dose-dependent manner, with the greatest benefit in the ²²⁵Ac + ICI group at 15 Gy. Treatment activated type I interferon signaling and increased MHC-I and PD-L1 expression. Notably, ⁹⁰Y reduced regulatory T cells, enhancing CD8⁺/Treg ratios, while ²²⁵Ac induced robust interferon-driven activation. Radionuclide selection and absorbed dose critically shape immune and therapeutic outcomes of antibody-based RPT combined with ICIs, underscoring the importance of delivery mechanism and dose optimization in combination therapy strategies. Full article

Purpose: This study aimed to compare QoL outcomes among patients undergoing active breathing control (ABC), voluntary deep inspiration breath hold (vDIBH), and surface-guided radiation therapy (SGRT). Methods: This was a non-randomized, three-arm clinical trial in which 55 patients were sequentially allocated to ABC (n = 19), SGRT (n = 20), or vDIBH (n = 16). QoL was assessed using the European Organization for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30) at baseline, treatment completion, and 6–8 weeks post-treatment. Linear regression was used to compare changed scales in QoL domains across groups. A p-value of <0.05 was considered statistically significant. Results: Baseline QoL scores were high across all groups, with physical functioning being the highest-rated domain and global health status the lowest. Fatigue, pain, and insomnia were the most highly reported symptoms at all time points. At 6–8 weeks, social functioning improved significantly in SGRT compared to vDIBH (16.67 vs. −12.50, p = 0.0053). Patients in the vDIBH group reported significantly increased pain compared to ABC at 6–8 weeks (p = 0.0240). No other significant differences were observed in QoL changes between the groups. Conclusions: The three breath-hold techniques maintained overall QoL with no differences between the groups, except for pain between vDIBH and ABC and social functioning for vDIBH and SGRT both at 6–8 weeks of follow-up. Despite the limitations of this study, each breath-hold technique has demonstrated comparable impact on QoL in patients with left-sided breast cancer and each could be used as a viable option with respect to QoL. Full article

Introduction. This study aims to conduct a cost-effectiveness analysis comparing two primary treatment approaches: radical prostatectomy versus radiotherapy plus androgen deprivation therapy (ADT) in patients with Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. Patients and Methods. Data were extracted from two published retrospective cohort studies. Using survival data from two retrospective studies, we reconstructed Kaplan–Meier curves, overlaid them for comparative metasurvival analysis, and developed a cost-function model to assess economic implications alongside clinical outcomes. The primary outcomes included biochemical recurrence-free survival (FFBF) at 2 and 5 years; the area under the survival curve; total cost per treatment strategy; and cost per recurrence-free patient at 5 years. Results. At 5 years, the estimated FFBF was 83% for radiotherapy vs. 28% for prostatectomy. Radiotherapy yielded an AUC of 80.7, while prostatectomy showed 41.9. Radiotherapy yielded a cost of 21,211 € per FFBF patient compared to 113,730 € for prostatectomy. Conclusion. Our study demonstrates that radiotherapy combined with ADT, when selected based on mpMRI stratification, may represent a cost-efficient alternative, pending prospective validation. To radical prostatectomy in patients with PI-RADS 5 prostate cancer, with a favourable cost–benefit profile. Full article

Radiation therapy (RT) has been one of the standard treatments for prostate cancer; however, its potential impact on nearby neural structures, such as the lumbosacral plexus (LSP), is often overlooked. The lack of contouring in treatment plans has led to unintended consequences. Radiation-induced lumbosacral plexopathy (RILSP) is a rare but serious complication that presents with progressive lower extremity sensory changes and weakness, mimicking radiculopathy. We report the case of a 66-year-old male who developed bilateral lower extremity neurological deficits post-pelvic radiation for prostate cancer. Radiographically, no compressive lesions were found, and the Electromyography (EMG) revealed involvement of nerves inconsistent with radiculopathy. This led to the diagnosis of RILSP. This case highlights the importance of recognition of RILSP in contrast to radiculopathy in patients with unexplained neurological symptoms after pelvic RT. This highlights the importance of incorporating the LSP as an organ at risk while planning for RT and reviewing retrospectively the dosimetry. It also emphasizes the need for improved contouring of LSP in radiation planning to minimize adverse effects. This sentiment is reflected in the literature, along with the consensus that more research is needed to address the true rate of RILSP. Full article

High doses of ionizing radiation during prenatal development can cause growth restriction, or a decrease in growth of the developing offspring. This outcome of intrauterine growth restriction (IUGR) can predispose the offspring to lifelong health outcomes, which is referred to as developmental programming. The role of the placenta in radiation-induced IUGR was investigated using a mouse model. Pregnant BALB/cAnNCrl mice were externally irradiated with 1.82 Gy x-ray irradiation on gestational day 14.5. Fetoplacental units were collected on gestational day 18.5, and growth restriction was observed in irradiated offspring. Whole placenta samples from growth restricted and sham-irradiated groups were analyzed via RNA-sequencing analysis. Differential gene expression (DEG) analysis revealed a total of 166 DEGs in the irradiated samples. Validation of these DEG findings were completed using RT-qPCR analysis. Gene ontology (GO) analysis of the DEGs supported the involvement of autoimmune response and dysregulation in retinol (vitamin A) metabolism in the placenta. Upstream prediction analysis identified a number of potential regulators responsible for the DEG profiles including Nppb, Myod1 and genes of the classic complement system (Complement C1q chains C1qa, C1qb, C1qc). Overall, these findings present an overview of the dysregulation in the mouse placenta following an acute, high-dose radiation exposure. Full article

Online adaptive radiotherapy mitigates errors in absorbed dose delivery due to daily anatomical changes during hypofractionated breast treatment, particularly when comprehensive nodal therapy includes the internal mammary chain. To illustrate this, we present a case of a 65-year-old woman with left-sided luminal B invasive carcinoma, who underwent segmentectomy and level 1–2 dissection. Pathology revealed an 18 × 15 × 13 mm primary tumor with lymphovascular invasion, two of eleven axillary nodes positive, and intramammary metastasis, staged pT1cN1a. She received adjuvant docetaxel–cyclophosphamide followed by letrozole. Hypofractionated radiotherapy (40 Gy in 15 fractions) was administered in an inspiration breath-hold setting using a CBCT-guided online-adaptive platform. Adaptive planning improved V95% coverage over the planned treatment for all targets: on average, whole breast coverage increased from 88.4% to 96.3%, supraclavicular from 93.0% to 97.1%, axilla from 90.6% to 96.7%, and internal mammary from 91.8% to 95.9%. Organ-at-risk metrics remained within limits: the mean heart dose increased slightly (from an average of 0.12 Gy in scheduled to 0.15 Gy in adaptive plans). At the same time, the LAD D0.03 cm³ decreased, and the heart V4 Gy fell modestly (from 13.3% in the scheduled plan to 8.2% in the adaptive plan), reflecting low-dose redistribution without exceeding constraints. Lung and thyroid mean doses remained comparable. The patient tolerated treatment well, with no acute toxicity or local recurrence. This case highlights the importance of daily adaptation for complex left-sided radiation treatment involving internal mammary nodes, demonstrating target recovery without exceeding absorbed dose constraints and supporting future studies on control, toxicity, and quality of life. Full article

Background: FLASH radiotherapy delivers ultra-high dose rates with normal tissue sparing, but mechanisms remain unclear. We present a streamlined workflow for establishing a LINAC-based electron FLASH (eFLASH) platform in low-resource settings without requiring vendor-proprietary hardware or software, or vendor-assisted modifications to broaden accessibility for FLASH studies. Methods: A LINAC was converted to eFLASH with pulse control and monitoring. Automatic frequency control (AFC) was optimized to stabilize dose per pulse (DPP). Beam data were measured with EBT-XD films, and a Monte Carlo (MC) model was commissioned for in vivo dose calculation. We demonstrated in vivo dosimetry in planning studies of mouse whole-brain and rat spinal cord (C1–T2) irradiation. We further assessed the impact of AFC optimization on the FLASH spinal cord study. Results: AFC optimization stabilized DPP at ~0.6 Gy/pulse, reducing large fluctuations under the default setting. MC agreed with measurements within 2% for PDDs and profiles. MC planning showed uniform whole-brain irradiation with 6 MeV FLASH, while the spinal cord study exhibited up to 10% dose fall-off within 1 cm along the cord, suggesting potential dose-volume effects confounding FLASH sparing. Following AFC optimization, 50% of the C1–T2 cord reached >133 Gy/s, a 23% increase versus default. Conclusions: We demonstrated a cost-effective eFLASH platform and verified its accuracy for preclinical studies, expanding the accessibility of FLASH research. Full article

Fractal dimension (Frac) and lacunarity (Lac) are frequently proposed as biomarkers of multiscale image complexity, but their incremental value over standardized radiomics remains uncertain. We position both measures within the Image Biomarker Standardisation Initiative (IBSI) feature space by running a fully reproducible comparison in two settings. In a baseline experiment, we analyze $N=1000$ simulated $64\times 64$ textured ROIs discretized to $N_g=64$, computing 92 IBSI descriptors together with Frac (box counting) and Lac (gliding box), for 94 features per ROI. In a wavelet-augmented experiment, we analyze $N=1000$ ROIs and add level-1 wavelet descriptors by recomputing first-order and GLCM features in each sub-band (LL, LH, HL, and HH), contributing $4\times (19+19)=152$ additional features and yielding 246 features per ROI. Feature similarity is summarized by a consensus score that averages z-scored absolute Pearson and Spearman correlations, distance correlation, maximal information coefficient, and cosine similarity, and is visualized with clustered heatmaps, dendrograms, sparse networks, PCA loadings, and UMAP and t-SNE embeddings. Across both settings a stable two-block organization emerges. Frac co-locates with contrast, difference, and short-run statistics that capture high-frequency variation; when wavelets are included, detail-band terms from LH, HL, and HH join this group. Lac co-locates with measures of large, coherent structure—GLSZM zone size, GLRLM long-run, and high-gray-level emphases—and with GLCM homogeneity and correlation; LL (approximation) wavelet features align with this block. Pairwise associations are modest in the baseline but become very strong with wavelets (for example, Frac versus GLCM difference entropy, which summarizes the randomness of gray-level differences, with $\left|r\right|\approx 0.98$; and Lac versus GLCM inverse difference normalized (IDN), a homogeneity measure that weights small intensity differences more heavily, with $\left|r\right|\approx 0.96$). The multimetric consensus and geometric embeddings consistently place Frac and Lac in overlapping yet separable neighborhoods, indicating related but non-duplicative information. Practically, Frac and Lac are most useful when multiscale heterogeneity is central and they add a measurable signal beyond strong IBSI baselines (with or without wavelets); otherwise, closely related variance can be absorbed by standard texture families. Full article

Prostatic artery embolization (PAE) is increasingly used as a primary minimally invasive treatment modality for lower urinary tract symptoms associated with benign prostatic hyperplasia. As a complex, fluoroscopic-guided endovascular procedure, PAE necessitates a significant use of ionizing radiation, raising important safety considerations for both patients and medical personnel. The objective of this review is to first summarize the procedural and anatomic fundamentals of PAE, and then to provide a comprehensive overview of the current literature on radiation dosimetry, establish contemporary benchmarks for dose metrics, and present an evidence-based guide to practical dose optimization strategies. Through a thorough review of published clinical studies, this article synthesizes reported values for key radiation indices, including Dose Area Product (DAP), Cumulative Air Kerma (CAK), and Fluoroscopy Time (FT). Furthermore, we will critically examine factors influencing dose variability—including patient complexity, procedural technique, and imaging technology—and will provide a practical, clinically oriented guide to implementing dose-saving measures. Ultimately, this review concludes that while PAE involves a non-trivial radiation burden, a thorough understanding and application of optimization principles can ensure the procedure is performed safely, reinforcing its role as a valuable therapy for BPH. Full article

In large-scale radiological events, there is a need to triage affected individuals based on their biological absorbed dose. Biodosimetry measures biological responses in relation to the received dose. Radiation-responsive protein biomarkers in peripheral blood lymphocytes, especially intracellular proteins, have been validated for biodosimetry with immunochemical-based measurement methods. However, these antibody-based assays can suffer from stability and batch-to-batch variations. Aptamers are single-stranded oligonucleotide alternatives to antibodies that are stable and much smaller in size, making them ideal probes for intracellular targets. However, few aptamers have been developed against intracellular targets, and these efforts are especially hampered due to the time-consuming nature of the conventional aptamer selection method. An efficient method for isolating aptamers against intracellular radiation-responsive proteins is not available yet. Herein, we used a microfluidic aptamer isolation method to develop an aptamer against the intracellular radiation biomarker BAX in blood lymphocytes. The isolated aptamer has a dissociation constant of 6.95 nM against human BAX protein and a bright detail similarity score of 1.9 when colocalizing with anti-BAX aptamer intracellularly. The in situ labeling of the intracellular BAX protein also shows the aptamer can be used to differentiate 2.5 Gy or 3 Gy of radiation in ex vivo human and in vivo mouse peripheral blood samples exposed to X-rays. In conclusion, this proof-of-concept study indicates that the microfluidic-enabled aptamer isolation method could be used for the development of a panel of targeted intracellular proteins for radiation biodosimetry applications. Full article

Radiotherapy employs high-energy X-rays to precisely target tumor tissues while minimizing damage to the surrounding healthy structures. Although its clinical efficacy is well established, the immunomodulatory effects of ionizing radiation remain complex and context-dependent. This study investigated the biological effects of radiotherapeutic doses on immune cells by evaluating lymphocyte viability, phenotypic profiles, and cytokine expression levels. Peripheral blood mononuclear cells (PBMCs) were isolated from six healthy donors and irradiated with 0, 2, or 6 Gy using a 6 MV linear accelerator (LINAC). Dose validation with an ionization chamber demonstrated strong agreement between estimated and measured values (intraclass correlation coefficient = 1, 95% CI). Immune subsets, including T cells (CD3+), helper T cells (CD3+CD4+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+CD4+Foxp3+), and natural killer (CD3-CD56+) cells, along with intracellular cytokines interleukin-12 (IL-12) and interferon-gamma (IFN-γ), were analyzed via flow cytometry at multiple time points. The results showed a significant, dose-dependent decline in overall lymphocyte viability (p < 0.01) compared to control. Cytotoxic T cells were the most radiosensitive, followed by helper and regulatory T cells, while NK cells were the most radioresistant. IL-12 expression initially increased post-irradiation, while IFN-γ levels remained variable. These findings demonstrate that radiation induces distinct alterations in immune phenotypes and cytokine profiles, which may shape the immune response. Immune profiling following irradiation may therefore provide valuable insights for optimizing combination strategies that integrate radiotherapy and immunotherapy in cancer treatment. Full article

Chronic pelvic neuropathies involving the pudendal, ilioinguinal, and genitofemoral nerves are a major source of refractory pain and disability, yet conventional steroid injections typically provide only short-lived benefit. We retrospectively analyzed 78 patients: 49 with pudendal neuralgia treated by pulsed radiofrequency and 29 with ilioinguinal (n = 15) or genitofemoral (n = 14) neuropathies treated by continuous radiofrequency ablation. For pudendal neuropathy, pRF provided a mean pain relief of 9.48 ± 9.52 weeks versus 3.98 ± 3.56 weeks after the first steroid injection and 3.32 ± 3.21 weeks after the most recent (p < 0.0001 for both). Quality-of-life scores improved significantly through 3 months, and analgesic use declined during this period. No correlation was found between symptom duration and treatment response. For ilioinguinal and genitofemoral neuropathies, cRFA extended pain relief to 21.76 and 17.68 weeks, respectively. Mean VAS scores improved from 6.87 to 1.73 for ilioinguinal (p < 0.0001) and from 6.36 to 2.36 for genitofemoral (p = 0.0007) neuropathies. Quality-of-life scores improved through 3 months, with trends toward baseline by 6 months, while analgesic use decreased initially before returning to baseline. Across all nerves, no major complications occurred. Radiofrequency treatment offers safe, longer-lasting relief than steroid injections for refractory pelvic neuropathies. Full article

Exposure to ionising radiation may be hazardous to living beings, including humans. Ionising radiation exposure has been shown to cause hepatic dysfunction or even liver cancer in persons receiving radiation therapy who do not have liver disease. Changes in hepatic enzyme values may suggest radiation-induced stress on liver cells. Then this experimental study examined the effect of different doses of radiation on the liver enzymes aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT). Methods: Six equal groups of thirty-six New Zealand white rabbits weighing 3 and 5 kg each were formed. The rabbits received total body radiation doses of 0 Gy (Control group), 0.053 Gy, 0.11 Gy, 0.21 Gy, 0.42 Gy, and 0.84 Gy on days, 1, 3, and 5 and week 1, week 2, week 3, and week 4. Generalised Linear Mixed Models (GLMMs) were used to compare the data statistically. Results: There was a significant rise in the serum liver enzyme levels; aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) all showed a statistically significant time effect after the application of different radiation doses. Based on the group effect of radiation, AST and ALP, but not ALT, showed statistically significant findings. Full article