Radiation, Volume 5, Issue 2 (June 2025) – 12 articles

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

Background: Patients with advanced breast cancer (BC) may be treated with stereotactic ablative radiotherapy (SABR) for tumor control. Variable treatment responses are a clinical challenge and there is a need to predict tumor radiosensitivity a priori. There is evidence showing that tumor infiltrating lymphocytes (TILs) are markers for chemotherapy response; however, this association has not yet been validated in breast radiation therapy. This pilot study investigates the computational analysis of TILs to predict SABR response in patients with inoperable BC. Methods: Patients with inoperable breast cancer (n = 22) were included for analysis and classified into partial response (n = 12) and stable disease (n = 10) groups. Pre-treatment tumor biopsies (n = 104) were prepared, digitally imaged, and underwent computational analysis. Whole slide images (WSIs) were pre-processed, and then a pre-trained convolutional neural network model (CNN) was employed to identify the regions of interest. The TILs were annotated, and spatial graph features were extracted. The clinical and spatial features were collected and analyzed using machine learning (ML) classifiers, including K-nearest neighbor (KNN), support vector machines (SVMs), and Gaussian Naïve Bayes (GNB), to predict the SABR response. The models were evaluated using receiver operator characteristics (ROCs) and area under the curve (AUC) analysis. Results: The KNN, SVM, and GNB models were implemented using clinical and graph features. Among the generated prediction models, the graph features showed higher predictive performances compared to the models containing clinical features alone. The highest-performing model, using computationally derived graph features, showed an AUC of 0.92, while the highest clinical model showed an AUC of 0.62 within unseen test sets. Conclusions: Spatial TIL models demonstrate strong potential for predicting SABR response in inoperable breast cancer. TILs indicate a higher independent predictive performance than clinical-level features alone. Full article

Humans are constantly exposed to low doses and low-dose rates of ionizing radiation from both natural and man-made sources. For this reason, there is a growing interest in studies on the biological effects of low-dose radiation. Vibrational spectroscopies, such as Fourier transform infrared and Raman micro-spectroscopies, have been fruitfully employed for studying the effects of high doses of ionizing radiation on biosystems. Aiming at clarifying the potential of the above-mentioned spectroscopic techniques to monitor the changes induced in cells, tissues, and other biological samples by low doses of ionizing radiations, we report a review of the literature in this research field. The analysis of published results suggests that vibrational spectroscopies make a valuable contribution. Additional and more systematic investigations could help to fully exploit the capabilities of these spectroscopic techniques. Full article