Radiation

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

Oral squamous cell carcinoma (SCC) is typically found in middle-aged or elderly individuals, is more common in men than women, can occur at any mucosal site, and is associated with a poor prognosis. The primary risk factors for oral SCC include the use of tobacco, betel nut, or areca nut, and excessive alcohol consumption. A comprehensive management plan for oral SCC typically involves a multidisciplinary team approach with surgery being the primary treatment approach, with or without radiotherapy. Radiotherapy is an essential component in the management of oral SCC, with its application guided by both tumour- and patient-related factors. It may be employed as a definitive, adjuvant, or palliative modality, depending on tumour stage, resectability, surgical margins, histopathological characteristics, as well as the patient’s overall health, financial considerations, and personal preferences. Effective radiotherapy for oral SCC inevitably leads to various tissue toxicities, which can vary among patients. These variations are primarily influenced by patient-specific characteristics, tumour-specific factors, and aspects related to the radiotherapy itself. Some of the complications resulting from ionizing radiation (IR) include oral mucositis, facial dermatitis, salivary gland dysfunction, trismus, and osteoradionecrosis, along with their management strategies. Full article

The Klein–Nishina formula is used to calculate and investigate the electronic cross-section, atomic cross-section, and Compton mass attenuation coefficients for the human blood, breasts, eye lens, ovaries, and testis, using X-rays in the 0.1–20 MeV energy range. The effects of radiation energy, tissue effective charge number, tissue density, and tissue electronic density on these parameters were studied. The results show that the electronic cross-section and atomic cross-section decrease with increasing radiation energy. These parameters are found to be linearly increasing when the density and electron density of a tissue increase. This increase is more rapid with a bigger slope when the electron density increases as compared to the density of each tissue. A complex relationship between these coefficients and the effective charge number Z_eff of tissues is observed because Z_eff changes with the energy and linear attenuation coefficient of a tissue. The Compton mass attenuation coefficient is found to be dependent on the effective charge number to mass number ratio Z_eff/A_eff instead of just the effective charge number. This increase in the Compton mass attenuation coefficient with increasing Z_eff/A_eff is rapid for the lower values of Z_eff/A_eff. However, for a higher Z_eff/A_eff ratio, the increase is very slow and becomes almost constant for X-ray energies above 10 MeV. The calculated parameters are useful in determining radiation dose for the investigated tissues and their response to low and high-energy X-rays. The results and outcomes are also very useful in shielding and protecting tissues from the hazards of radiation. These parameters are also helpful in determining the scattered and optimum doses to improve image quality and treatment options in radiology and radiation therapy to offer the best care. Full article

Background: Delays in breast cancer treatment negatively affect prognosis and have increased over time. Data on waiting times in Switzerland are limited. Patients and Methods: This study analyzed cancer registry data from 2003 to 2005 (2628 patients) and 2015 to 2017 (421 patients) to evaluate waiting times for diagnosis, surgery, and radiotherapy; temporal trends; and survival in women with stage I–III invasive breast cancer treated with surgery without chemotherapy. Associations with demographic/clinical factors and overall survival (OS) were assessed using ANOVA, uni-/multivariable regression, Kaplan–Meier, and Cox regression. Results: From 2003 to 2005, mean intervals were biopsy-to-diagnosis 4.3 days, diagnosis-to-surgery 18.8 days, biopsy-to-surgery 26.8 days, and surgery-to-radiotherapy 56.7 days. Longer diagnosis-to-surgery times were associated with metropolitan areas, public hospitals, basic insurance, mastectomy, and older age (all p < 0.001). Radiotherapy delays were also longer in metropolitan areas and after mastectomy (p < 0.001). Between 2003–2005 and 2015–2017, diagnosis-to-surgery times rose in Eastern Switzerland (from 21.3 to 31.2 days), while radiotherapy timing remained stable. Five-year overall survival improved (from 76.7% to 88.4%), but was not significantly impacted by diagnosis-to-surgery intervals. Conclusions: Despite timely surgery in Switzerland (2003–2005), disparities existed, and time to surgery increased by 2015–2017. Reducing waiting times remains important despite no significant short-term OS impact. Full article

Background: We present the implementation of an in vivo dosimetry program that enhances treatment setups, ensuring high accuracy that is needed globally. This approach proves valuable in smaller departments by helping to detect and prevent errors. Evaluation studies have shown that in vivo dosimetry is a reliable method for assessing the overall accuracy of treatment delivery. Methods: Comprehensive development and validation of an in vivo dosimetry program using silicon diodes, ionization chambers, and calibrated electrometers for accurate radiation in dose measurements for treatments involving Co-60 or 6 MV X-ray beams. Results: The outcomes demonstrated that all diodes were dependable, with deviations of less than 1% (0.89 ± 0.10 cGy). Calibration curves were generated, showing dose variations of only 0.13% in the diode readings. The overall analysis revealed a mean deviation of up to 1%. Conclusions: These results provide a thorough assessment for patients’ treatment and facilitate timely interventions when needed, helping to ensure that dose variations stay within acceptable limits. Full article

Microdosimetry plays a critical role in particle therapy by quantifying energy deposition within microscopic domains to assess biological effects. This study evaluates the influence of different microdosimetric functions (MFs) and domain geometries (DGs) on relative biological effectiveness (RBE) predictions in carbon ion radiotherapy. Specifically, we compare the analytical microdosimetric function (AMF), calculated for spherical domains and implemented in PHITS, with the Kiefer–Chatterjee (KC) track structure model, which is conventionally applied to cylindrical geometries. To enable a direct comparison, we also introduce a novel implementation of the KC model for spherical domains. Using both models, specific energy distributions were calculated across a range of domain sizes and geometries. These distributions were input into the modified microdosimetric kinetic model (mMKM) to calculate RBE for the HSG cell line and compared against published in vitro data. The results show that both microdosimetric function and domain geometry significantly affect microdosimetric spectra and the resulting RBE, with deviations exceeding 10% when fixed mMKM parameters are used. Parameter optimization within the mMKM enables alignment across models. Our findings emphasize that microdosimetric function and domain geometry selection must be explicitly accounted for in microdosimetry-based RBE modeling, and that model parameters must be tuned accordingly to ensure consistent and biologically accurate predictions. Full article

The number of server failures, including those in radiotherapy, has dramatically increased over the past 5 years, primarily due to cyberattacks. Despite this trend, many clinics remain unprepared to handle such situations effectively. While it is possible to resolve these issues with thorough preparation and dedicated effort without causing significant interruptions to patient treatments, the process is considerably easier if numerous steps and analyses, both technical and clinical, have already been undertaken. This preemptive work allows for quicker responses and a faster resumption of patient treatments. There are established guidelines on how to prioritize patients and manage total dose in the event of multiple missed treatment sessions. However, many radiotherapy departments in Germany still lack individualized plans for handling software failures. In this article, we describe a failure of the radiotherapy OIS (ARIA by Varian) caused by an interface failure in the Central IT department of the clinic. From this event, we developed a clinical guideline for addressing issues during the outage and identified clinical processes that can be implemented in advance. Our focus was particularly on handling the large volumes of data involved in organizing patient treatments and scheduling. Overall, there needs to be a cultural shift in both the development of technical server infrastructures and the approach to managing OIS failures, as the likelihood of such events increases along with the negative impacts due to increasingly complex treatment plans and software landscapes. Full article

Low-dose radiotherapy had historically been used to treat both bacterial and viral pneumonias. In the present day, this is not in use due to the development of antibiotics and other supportive measures as well as a concern regarding late radiation toxicities. COVID-19 presented us with a novel respiratory illness without a strong evidence-based best practice; it was thought, therefore, that there may be a role for low-dose radiotherapy in the absence or failure of a standard treatment. The rationale for this was based around the ability of low-dose radiation to reduce an inflammatory state. We treated two individuals suffering from severe COVID-19 with low-dose whole lung radiotherapy, in the setting of a phase I trial. Both patients improved clinically, biochemically, and radiologically within a matter of days. We discuss why the meta-analyses may not have shown this advantage. Full article

This study aimed to evaluate the characteristics of short acquisition times using the Clear adaptive Low-noise Method (CaLM) and Advanced intelligent clear-IQ engine (AiCE) reconstructions in a semiconductor-based positron emission tomography (PET)/computed tomography system. PET data were acquired for 30 min in list mode and resampled into time frames ranging from 15 to 120 s. Images were reconstructed using three-dimensional ordinary Poisson ordered-subset expectation maximization (OSEM) with time of flight (TOF) and OSEM with TOF and point spread function modeling (PSF) algorithms, with OSEM iterations adjusted from 1 to 20 and CaLM applied under Mild, Standard, and Strong settings. AiCE reconstruction allows for the modification of only the acquisition time. The images were evaluated based on the coefficient of variation, recovery coefficient, % background variability (N_10mm), % contrast-to-% background variability ratio (Q_H10mm/N_10mm), and contrast-to-noise ratio. While OSEM with TOF reconstruction did not significantly reduce the acquisition time, the addition of PSF correction suggested the potential for further reduction. Given that the AiCE characteristics may vary depending on the equipment used, further investigation is required. Full article

Objective: Radiotherapy administered to control thoracic cancers results in a partial irradiation of the heart at mean doses up to 19 Gy, which increases the risk of developing a spectrum of cardiovascular diseases known as radiation-induced heart disease (RIHD). As inflammation is a major driver of the development of RIHD, we investigated the potential of the anti-inflammatory agent cannabidiol (CBD) to attenuate irradiation-induced cardiovascular damage in vivo. Methods: Female C57BL/6 mice were given daily injections of CBD (i.p., 20 mg/kg body weight) for 4 weeks beginning either 2 weeks prior to 16 Gy irradiation of the heart or at the time of irradiation. Mice were sacrificed 30 min and 2, 4, and 10 weeks after irradiation to investigate the expression of inflammatory markers and stress proteins in primary cardiac endothelial cells (ECs). DNA double-strand breaks, immune cell infiltration, and signs of fibrosis were studied in explanted heart tissue. Results: We showed that the irradiation-induced upregulation of the inflammatory markers ICAM-1 and MCAM was only attenuated when treatment with CBD was started 2 weeks prior to irradiation but not when the CBD treatment was started concomitant with irradiation of the heart. The protective effect of CBD was associated with a decrease in irradiation-induced DNA damage and an increased expression of protective heat shock proteins (Hsp), such as Hsp32/Heme-oxygenase-1 (HO-1) and Hsp70, in the heart tissue. While the upregulation of the inflammatory markers ICAM-1 and MCAM, expression was prevented up to 10 weeks after irradiation by CBD pre-treatment, and the expression of VCAM-1, which started to increase 10 weeks after irradiation, was further upregulated in CBD pre-treated mice. Despite this finding, 10 weeks after heart irradiation, immune cell infiltration and fibrosis markers of the heart were significantly reduced in CBD pre-treated mice. Conclusion: CBD treatment before irradiation mediates beneficial effects on murine hearts of mice, resulting in a reduction of radiation-induced complications, such as vascular inflammation, immune cell infiltration, and fibrosis. Full article

The number of chromosomal aberrations induced by a whole-body uniform exposure to ionizing radiation is typically assumed to follow a Poisson distribution. If this exposure is partial, the zero-inflated Poisson model is appropriate to describe the yield of chromosomal aberrations. In this work, two different Bayesian posterior approaches (numerical integration and Laplace’s approximation) for zero-inflated Poisson responses are studied for cytogenetic biodosimetry dose estimation purposes. They are evaluated using two experiments from the literature, both of which include data for dose–response calibration and the simulation of partial-body exposure. Laplace’s approximation demonstrates strong performance, delivering rapid results with a loss of precision that may not significantly impact clinical measurements compared to those obtained through the more computationally intensive numerical integration approach. Full article

This study explores the change in inflammatory markers over the course of neoadjuvant chemoradiation and adjuvant chemotherapy for LARC and assesses the association with clinicopathological factors at pre-specified time-points. We examined the trends of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), carcinoembryonic antigen (CEA), fibrinogen, and albumin through multilevel modelling of 29 prospective LARC patients across six time-points: before neoadjuvant chemoradiation (T1), week 3 of chemoradiation (T2), post-chemoradiation (T3), post-surgery (T4), midpoint of adjuvant chemotherapy (T5), and chemotherapy completion (T6). Variables collected included ethnic background, body mass index (BMI), smoking status, and pathological responses graded by Ryan tumour regression grade and pathological tumour and nodal status. NLR and PLR demonstrated an increasing trend during chemoradiation. Median CEA was highest at baseline and lowest at T4. The highest median values for NLR, PLR, CRP, and fibrinogen were at T4. Smokers demonstrated a trend towards a higher NLR compared to non-smokers. NLR was significantly higher in Caucasians compared to Asians at T2. Patients with pathological node-negative status had a higher NLR at T5 and T6 and a higher PLR at T1, T3, T5 and T6. Overall, inflammatory indices change dynamically throughout treatment and vary with clinicopathological factors. Full article

The aim of this work was to investigate the relationship between the growth rate of tumor cells and their fractionation gain. Two head and neck squamous cell carcinoma (HNSCC) cell lines, one human papillomavirus (HPV) negative (HPV−) and one HPV+, and a primary fibroblast cell line were supplemented with four different concentrations of fetal bovine serum (FBS) to achieve different division rates. The effect of five different fractionation regimens was studied, namely 1 × 10 Gy, 2 × 5 Gy, 3 × 3.3 Gy, 4 × 2.5 Gy, and 5 × 2 Gy. Survival was studied using the colony-forming assay. Different concentrations of FBS were used to achieve different doubling rates for all cell lines. The HPV+ cell line was significantly more sensitive to radiation than the HPV− cell line in all fractionation schemes. The fibroblast cell line was less sensitive at low fractionation compared to the tumor cell lines. Low fractionation had a significantly higher effect, except for 5 × 2 Gy fractionation, which had a higher effect than 4 × 2.5 Gy. The number of radiosensitive mitoses during irradiation in the fractionation scheme could not explain the higher effect of 5 × 2 Gy. There was no difference in survival with the four different concentrations of FBS in all three cell lines and different fractionations. The doubling time (DT) rates of cell lines resulting from FBS deprivation do not reflect the expected increased radiation sensitivity of rapidly dividing cells. Full article

This article explores the implementation of Cesium-131 brachytherapy in veterinary academia, challenging the prevailing use of external beam therapy for small animal brain tumors. The authors report on the first ever canine patient treated with Cesium-131. While recent advances like intensity-modulated and stereotactic radiation therapies gain ground, brachytherapy remains underutilized in veterinary practice, primarily due to regulatory hurdles. In contrast, Cesium-131 brachytherapy, widely adopted in human medicine for neoplasia within the brain, presents advantages such as a short half-life, low kilovolt emission, and enhanced safety. Motivated by the need to eliminate post-surgery radiation delays, our academic center undertakes Cesium-131 brachytherapy for small animals, aiming to gather preliminary clinical data on disease-free intervals and survival rates. Comparative analyses against historical external beam therapy data may offer insights applicable to the human neuro-radiation community. Additionally, the technique’s implementation could initiate preclinical platform for combined intracavitary treatments, particularly immunotherapy, leveraging brachytherapy’s spatial dose distribution heterogeneity to influence the tumor microenvironment and enhance the immune response. The authors outline the adaptation of the technique on a canine glioma patient to provide preliminary feasibility results, describe the principal indications and outcomes of Cesium-131 for human brain tumors, and discuss prospects for advancing veterinary neuro-brachytherapy. Full article