Radiation doi: 10.3390/radiation6030031

Authors: Antonio Marzano Martina Pacillo Giovanni Gagliardo di Carpinello Marta Ascione Claudia Panzano Alessia Di Girolamo Rocco Cangiano Francesca Miceli Luca di Marzo Wassim Mansour

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.

Radiation doi: 10.3390/radiation6030030

Authors: Manuela Montatore Gianmichele Muscatella Ruggiero Tupputi Eluisa Muscogiuri Giuseppe Guglielmi

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.

Radiation doi: 10.3390/radiation6030029

Authors: Enrico Rosa Bruno Fionda Maria Vaccaro Valentina Lancellotta Elisa Placidi Maria Concetta La Milia Gabriele Ciasca Pierpaolo Dragonetti Andre Karius Frank-André Siebert Luca Tagliaferri Marco De Spirito

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.

Radiation doi: 10.3390/radiation6030028

Authors: Francis Chan Jay Black Peter Parashos

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.

Radiation doi: 10.3390/radiation6030027

Authors: Yonwaba Mzizi Bwalya Angel Witika Honest Ndlovu Mbongeni Shungube Pedzisai Makoni Sandile Sibiya Amanda Mdlophane Keamogetswe Ramonaheng Mike Sathekge Sipho Mdanda

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.

Radiation doi: 10.3390/radiation6030026

Authors: Erkan Topkan Doga Topkan Efsun Somay Duriye Ozturk Sibel Bascil Ugur Selek

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.

Radiation doi: 10.3390/radiation6030025

Authors: Flavio Donnini Giovanni Rubino Giuseppe Battaglia Pierpaolo Pastina Tommaso Carfagno Marta Vannini Alfonso Cerase Giulio Bagnacci Armando Perrella Salvatore Chibbaro Maria Antonietta Mazzei Paolo Tini

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.

Radiation doi: 10.3390/radiation6030024

Authors: Imen Hammami Omer A. Magzoub Asma Ayadi Faouzi Hosni Salam Labidi

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.

Radiation doi: 10.3390/radiation6030023

Authors: Lifeng Chen Li Wang Hamid A. Bakshi

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.

Radiation doi: 10.3390/radiation6030022

Authors: Jared Mount Brandon Mount Michael Rutenberg John A. Stauffer

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.

Radiation doi: 10.3390/radiation6020021

Authors: Shely Kagan Yulya Kagan Tharshini Yoganathan Madette Galapin Christina Yang Britney Zhang Shivani Verma Henry C. Y. Wong Amir H. Safavi Michael C. Tjong Shirley S. W. Tse Shing Fung Lee Sarah Bayrakdarian Edward Chow Irene Karam

Background: Radiation dermatitis (ARD), particularly its most severe form, moist desquamation (MD), is a frequent and distressing complication of external beam radiotherapy (RT) in head and neck (H&N) cancer patients. Standard management often provides limited benefit for healing and symptom control. Silicone-based foam dressings, including Mepilex Lite and Mepilex Ag, may offer atraumatic adherence, moisture balance, and pain reduction. This study evaluated their real-world effectiveness for MD after conventional RT. Methods: Ten H&N cancer patients with clinically confirmed MD post-radiotherapy were prospectively followed until healing. Patients received Mepilex Lite or Mepilex Ag based on exudate level and infection risk, with dressings changed every three days. Patient- and healthcare provider-reported measures were collected throughout follow-up. The primary endpoint was time to MD resolution, defined as healing to grade 1 skin status. Secondary endpoints included changes in symptom burden, dressing tolerability and satisfaction, and adverse events. Results: Median age was 69 years (range 44–78). All wounds healed to grade 1, with a mean time of 8.6 days (SD 3.9). No infections or adverse events occurred. Pain, burning, and interference with daily activity decreased, and most patients reported improved comfort. Conclusions: In this small prospective cohort study, use of Mepilex dressings was associated with rapid healing, good tolerability, and improvement in patient-reported symptoms of acute radiation dermatitis. These findings suggest that Mepilex dressings may be a promising management option and warrant evaluation in larger comparative studies.

Radiation doi: 10.3390/radiation6020020

Authors: Leila T. Tchelebi Janice Lester Joshua J. Kim Huaizhi Geng Ying Xiao

Radiation therapy quality assurance (RTQA) is critical to the success of RT and impacts trial outcomes. We aimed to evaluate the existence of standardized quantitative metrics to grade contours as part of RTQA and to identify barriers to standardization. A systematic review was conducted according to PRISMA guidelines. PubMed, Web of Science, and Embase were used to search relevant studies published from 2014–2024. Our endpoints were quantitative metrics used to guide contour scoring. We initially planned quantitative synthesis (meta-analysis) of geometric metric distributions across studies. However, the heterogeneity in evaluation methods, predominance of qualitative assessment, and lack of standardized reporting precluded meaningful quantitative pooling. We therefore performed structured qualitative synthesis, thematic analysis, and gap assessment. A total of 37 studies were included, 20 of which were prospective and 17 were retrospective. Of the prospective, 12 reported the results of benchmark case/dummy run reviews, 4 were a combination of benchmark case/dummy runs and individual QA analyses done pre- or post-treatment, 1 used knowledge-based planning to evaluate plans in real-time, and 3 involved real-time prospective QA. Only one reported the use of an objective QA scoring system. There is a concerning lack of standardized quantitative metrics to evaluate RT contours on clinical trials and a lack of methodological consistency required for systematic quantitative synthesis, reinforcing the need for standardization. Effort is needed to create guidelines for quantitatively evaluating RT contours to use across clinical trials to improve the quality and validity of RTQA.

Radiation doi: 10.3390/radiation6020019

Authors: Dusan Milanovic Tatiana Lushchaeva Hai Minh Ha Raul-Ciprian Covrig Christian Scheller Klaus-Peter Stein I. Erol Sandalcioglu Antje Wiede André Glowka Daniel Medenwald

Preclinical studies and data from other cancers suggest that inhibition of the Hedgehog (Hh) pathway also has antiproliferative effects on glioma cells. A key component of this pathway is the Smoothened (SMO) protein, which is expressed in high-grade gliomas. Itraconazole (ITRA), a widely used antifungal agent, inhibits SMO, the PI3K/AKT/mTOR pathway, and the VEGF/VEGFR-2 axis—both of which are critical for GBM progression and angiogenesis. This protocol describes a prospective, single-center, dose-escalation phase I study with the classical 3 + 3 design in order to determine the MTD of ITRA. The study enrolls patients with a newly histologically confirmed diagnosis of GBM, without previous treatment except surgery. They will be treated with standard RT schedule (60 Gy in 30 fractions) with concurrent TMZ 75 mg/m2 and ITRA 2 × 100 mg, 200 mg, or 300 mg daily. The primary endpoint is to determine the MTD of ITRA given concurrently with RT + TMZ. Secondary endpoints include safety and tolerability of ITRA, overall survival (OS), progression-free survival (PFS), overall objective response rate, use of corticosteroids, treatment compliance, and health-related quality of life (EORTC QLQ-C30 and BN20). Participants will be monitored for one week post-treatment. All relevant statistics will be primarily descriptive.

Radiation doi: 10.3390/radiation6020018

Authors: Ugur Yilmaz Ellen Jones Lawrence B. Marks

This study aims to evaluate the quantitative impact of FDG-PET on detecting extra-pelvic metastases in women with cervical cancer, using population-based data, following its approval by US Medicare/Medicaid in 2005 for staging patients without detectable extra-pelvic metastases on CT or MRI scans. Surveillance, Epidemiology, and End Results (SEER) data from eight US registries from 1975 to 2021 were analyzed. The proportions of synchronous metastases “Synchronous/(Synchronous + Metachronous)” were compared between the pre-PET era (1995–1999 and 2000–2004) and the PET era (2010–2014). The estimated fraction of extra-pelvic metastases at initial diagnosis was 35% in the pre-PET era (2000–2004) compared to 46% in the PET era (2010–2014) (absolute difference 11%; p < 0.001). The proportion of undetected metastases decreased from 65% to 54%, indicating that PET identified up to 17% (i.e., [65 − 54]/65) of previously undetectable subclinical metastases. Likewise, the comparison of data from 1995–1999 vs. 2010–2014 showed 29% vs. 46% (absolute difference 17%; p <0.001). The proportion of undetected metastases decreased from 71% to 54%, suggesting that PET identified up to 24% (i.e., [71 − 54]/71) of the previously undetectable subclinical extra-pelvic metastases. In conclusion, up to ≈17–24% of subclinical extra-pelvic metastases, previously undetectable at initial diagnosis, appear to be identified through PET, findings that are consistent with and externally validate our prior population-based observations in non-small cell lung cancer.

Radiation doi: 10.3390/radiation6020017

Authors: Laura Eling Liam Day Micah Barnes Matthew Cameron Michael De Veer My-Linh Tempo Helen Forrester Mitzi Klein Daniel Hausermann Jean A. Laissue Raphaël Serduc

Microbeam Radiation Therapy (MRT) is a drastically novel approach of radiosurgery, challenging the understanding of how normal tissues respond to radiation therapy, where X-rays generated by a synchrotron light source are collimated into wafers of high-dose (hundreds of Gray), thin (50 µm) parallel microbeams. Recent work showed that MRT dose prescription must consider a dual approach: separating normal tissue dose constraints tied to the valley dose prescription and anti-tumor effects, depending on the prescribed number of ports. Here, we consolidate this assumption by increasing the number of MRT incidences to irradiate 9L-bearing rats with a cumulated valley dose of 10 Gy. 9L-bearing rats were irradiated by eight ports of conventional Broad Beam (BB) or MRT. Animals were followed up clinically by MR imaging, histopathology and survival analysis. MRI follow-up revealed that MRT significantly amplified antitumor effect and tumor tissue damage while improving the clinical score of animals. Ten Gy, delivered by either BB or MRT, increased median survival time to 15 and 39.5 days after irradiation, respectively. Neither complete ablation of brain tumors nor long-term survival was achieved, but multiport MRT (eight ports) showed an outstanding dose equivalence factor (×2.9), which needs to be tested in a clinical environment.

Radiation doi: 10.3390/radiation6020016

Authors: Muhammad Kabir Abdullahi Arbab Sufyan Wadood Md Serajun Nabi Sarina Binti Mansor Mohammad Faizal Ahmad Fauzi

Background: Nasopharyngeal carcinoma (NPC) presents significant diagnostic and therapeutic challenges, often due to late-stage detection and its complex anatomical location. The increasing integration of artificial intelligence (AI) into oncology offers potential opportunities to enhance the precision of NPC management. This systematic review aims to synthesise the current evidence of AI applications in NPC diagnosis, prognostication, and treatment planning. Methods: A systematic literature search was conducted following PRISMA guidelines across multiple databases (PubMed, Scopus, Embase, Google Scholar, IEEE Xplore) for studies published up to June 2025. From an initial pool of 2549 articles, 55 studies meeting the inclusion criteria were selected for qualitative analysis. The review focuses on AI models applied to key diagnostic modalities: computed tomography (CT), magnetic resonance imaging (MRI), and histopathological whole-slide images (WSI). Results: AI, particularly deep learning (DL), shows promising performance in automating critical tasks across all modalities. For CT and MRI, models have been reported to achieve accurate tumor and organ-at-risk segmentation, potentially supporting radiotherapy planning, and show strong performance in predicting survival outcomes and treatment toxicity. In digital pathology, AI enables automated diagnosis and facilitates the extraction of prognostic “pathomic” features from WSIs, with some studies suggesting performance comparable to or exceeding traditional radiomics. The most significant advances are seen in multimodal AI systems that integrate radiological, pathological, and clinical data, which, in some studies, show modest improvements in prognostic performance compared to single-modality approaches. However, these findings are preliminary, as none of the reviewed multimodal models underwent rigorous external validation in large, multi-center cohorts. Reported performance varies considerably across studies, and claims of superiority should be interpreted with caution.

Radiation doi: 10.3390/radiation6020015

Authors: Antonio Piras Albert Comelli Andrea D’Aviero Nino Dispensa Nicola Pavan Fabrizio Di Maida Davide Cusumano Calogero Casà Antonino Daidone Viviana Benfante Domenico Genovesi Tommaso Ingrassia Domenico Di Raimondo Antonino Tuttolomondo Luca Boldrini

Introduction: Radiotherapy (RT) plays a crucial role in the management of prostate cancer (PC). Artificial intelligence (AI) is reshaping cancer care by providing innovative tools for diagnosis, treatment optimization, and outcome prediction. This review provides an end-to-end synthesis of AI applications across the prostate RT workflow, critically evaluating their clinical maturity, level of evidence, and current barriers to real-world implementation. Methods: A literature review of PubMed/MEDLINE and Embase was conducted to investigate the impact of AI on prostate RT. Only original articles published up to 1 August 2025 were included. The 27 selected studies were categorized into the following clusters: adaptive radiotherapy, autocontouring, autoplanning, prediction, synthetic computed tomography (CT), quality assurance (QA), and tracking. Results: Autocontouring was the most represented cluster, followed by prediction, autoplanning, and adaptive RT. Fewer studies addressed tracking, QA, and synthetic CT. Conclusions: AI shows significant potential across multiple phases of the prostate RT workflow; however, most evidence is based on retrospective or technical validation studies. Further research is required to establish clinical benefit and support integration into personalized treatment strategies.

Radiation doi: 10.3390/radiation6020014

Authors: Chalina Huynh Pavanpreet Metley Kent Powell Matthew Larocque Keith Aronyk Alysa Fairchild

Background. Patients with malignant or benign central nervous system (CNS) tumours are evaluated for suitability of treatment modality based on multiple clinical and tumour-related factors. To obtain multidisciplinary consensus, a patient’s file and imaging are commonly reviewed by a tumour board (TB). There are three relevant weekly TB venues at our institute—gamma knife stereotactic radiosurgery (SRS) intake rounds, CNS rounds, and stereotactic body radiotherapy (SBRT) rounds—which are attended by non-overlapping clinician teams. We explored the clinical parameters prompting multiple TB reviews in patients with complex CNS tumours. Methods. Data were retrospectively obtained from electronic medical records. Patients referred for discussion at SRS rounds (November 2017–June 2020) were cross-referenced with those reviewed in CNS rounds and SBRT rounds. The cohort of interest included patients who underwent review at more than one TB for the same indication. Patient, tumour, and treatment factors were abstracted, and descriptive statistics were calculated. A sub-cohort of patients with pre-plans created for both SRS and conventionally fractionated external beam radiotherapy (EBRT) was identified. Dosimetric data were analyzed. Results. Of 1091 patients, 87 (8.0%) were discussed at more than one TB. 59/87 (67.8%) patients were reviewed at two TBs pertaining to the same CNS lesion and comprised the study cohort. The most common tumour type was meningioma (20/59), and the most common reason for multiple discussions was proximity to optic structures (19/59). After TB discussions, 25/59 patients were seen in consultation by one specialist, 29/59 by two, and 5/59 by none. Overall, the final treatment decisions were conventional EBRT in 21/59; SRS in 18/59; surveillance in 12/59; surgery in 3/59; systemic therapy in 3/59; proton referral in 1/59; and SBRT in 1/59. A total of 20/59 patients were treated with palliative intent. Among all patients who ultimately received radiotherapy, median interval between the first TB discussion and the first RT treatment was 56 days (IQR 7.5–65.5 d). The pre-plan sub-cohort consisted of four patients, all of whom were ultimately treated with conventional EBRT. Conclusions. Evidence to support optimal treatment for some complex CNS tumours can be limited. Multiple radiotherapy modalities may be equally favourable (or unfavourable) options. Proximity to the optic apparatus and previous CNS irradiation are common reasons for clinical equipoise. Tumour board review is an essential tool in formulating a multidisciplinary care plan; however, attention should be paid to ensuring that subsequent consultations and treatment initiation are not unduly delayed.

Radiation doi: 10.3390/radiation6020013

Authors: Jörg Andreas Müller Ramsia Geisler Janne Vehreschild Shimita Raquib Katharina Appel Charlotte Flasshove Steffi Ulrike Pigorsch Sina Pütz Christian Rafael Torres Reyes Christoph Römmele Margarete Scherer Christoph Stellbrink Daniel Medenwald

Background: Cancer patients receiving or having received radiotherapy (RT) represent a clinically vulnerable group during the COVID-19 pandemic. However, systematic data on their clinical course, comorbidities, and vaccination status are limited. The German National Pandemic Cohort Network (NAPKON), established to systematically collect comprehensive clinical data on COVID-19 patients nationwide, provides a unique opportunity to address this gap. This study aimed to describe radiation therapy patterns and COVID-19-related clinical characteristics among patients documented within the NAPKON Cross-Sectoral Platform (SUEP). Methods: This multicenter, descriptive analysis was conducted within the framework of the German National Pandemic Cohort Network (NAPKON). All patients with documented RT and confirmed SARS-CoV-2 infection were identified in the SUEP database. RT was classified relative to the documented infection date as occurring before, during, or after infection. Demographic, clinical, laboratory, imaging, and vaccination data were extracted and analyzed descriptively. Due to the small sample size, no correlation or multivariable analyses were performed. Results: A total of n = 90 patients were included in the analysis. The median age was 65 years (range 22–90), and 56% were male. Most patients (93%) received one course of RT, most frequently targeting specific organ systems (54%), while total body irradiation was performed in 4%. The median radiation dose was 45 Gy (IQR 30–60). Among 68 patients with evaluable timing information, RT had been administered before infection in 53 patients (77.9%), during infection in 3 patients (4.4%), and after infection in 12 patients (17.6%). At the time of SARS-CoV-2 detection, 76% of patients experienced a phase without complications, 19% a phase with complications, and 2% a critical phase. The majority of vaccinated individuals had received Comirnaty (BioNTech/Pfizer; 80%). COVID-19-typical findings were identified in 18% of chest X-rays and 27% of CT scans. Clinical and laboratory characteristics showed no substantial differences by hospital length of stay. Conclusions: Patients with documented RT and SARS-CoV-2 infection in the NAPKON registry predominantly experienced mild or moderate COVID-19 courses and showed a relatively high vaccination uptake. However, due to the descriptive study design and the absence of a control group, these findings should not be interpreted as being attributable to RT itself but rather as a characterization of this registry cohort. Importantly, the cohort mainly comprised patients with a history of RT before SARS-CoV-2 infection, whereas only a small minority received RT during infection. Although the analysis was descriptive and limited by missing data, it demonstrates the feasibility and scientific value of integrating oncologic subcohorts within national pandemic research networks. Continued longitudinal analyses will be essential to further characterize outcomes of patients with cancer and RT in future pandemics.

Radiation doi: 10.3390/radiation6010012

Authors: Jesús Antonio Lara-Reyes Libia Xamanek Cortijo-Palacios María Elena Hernández-Aguilar Gonzalo E. Aranda-Abreu Fausto Rojas-Durán

Cancer remains a significant global health burden, often requiring conventional treatments characterized by considerable side effects and limited tumor specificity. This review addresses the critical gap in understanding the non-thermal mechanisms by which Pulsed Electromagnetic fields (PEMFs) exert selective anti-tumor effects. Our primary objective is to analyze the molecular and cellular events through which low-intensity PEMF triggers stress responses and apoptosis in neoplastic cells without impacting normal cell viability. This comprehensive review synthesizes current evidence on the biological effects of PEMFs. Findings indicate that PEMFs disrupts intracellular homeostasis, induces reactive oxygen species-mediated oxidative stress, and activates endoplasmic reticulum stress, collectively driving malignant cells towards apoptosis or cell cycle arrest. Importantly, these effects are preferentially observed in cancer cells due to their inherent biophysical vulnerabilities—such as depolarized membrane potentials—and depend critically on specific PEMFs parameters. In conclusion, PEMFs acts as a multifaceted disruptor of cancer cell homeostasis, representing a promising non-invasive therapeutic modality. Further research is essential to optimize dosimetry and identify primary molecular sensors such as radical pair dynamics, to enhance clinical application and explore synergistic combinations with existing therapies.

Radiation doi: 10.3390/radiation6010011

Authors: Rusli Muljadi Lutfi Hendriansyah Patricia Diana Prasetiyo Gilbert Sterling Octavius

Background/Objectives: Hemangioblastomas are rare, benign, highly vascular tumors of the central nervous system, frequently associated with von Hippel–Lindau (vHL) disease. Case Presentation: We report a 16-year-old female with vHL presenting with recurrent headaches, abdominal distension, and ocular discomfort. Imaging revealed hemangioblastomas in the fourth ventricle and retrobulbar space, alongside multiple pancreatic cysts. The patient underwent three sessions of Gamma Knife Surgery (GKS) with initial tumor regression and symptom relief. However, long-term follow-up demonstrated progressive disease, with new lesions in the cerebellum, spinal cord, and orbit, including cystic transformation. Histopathology confirmed the reticular variant of hemangioblastoma. Despite further radiosurgical and surgical recommendations, the patient and family opted for conservative management, with lesions remaining radiographically stable over nine years. Conclusions: This case demonstrates that Gamma Knife Surgery may provide temporary local disease control for selected solid hemangioblastomas in von Hippel–Lindau disease but does not alter the underlying disease course. Long-term radiographic stability should be interpreted cautiously, as hemangioblastomas exhibit saltatory growth patterns that make it difficult to distinguish treatment effect from natural tumor quiescence. These findings emphasize that radiosurgery should be regarded as a disease-control strategy rather than curative therapy, underscoring the importance of individualized management, multidisciplinary decision-making, and prolonged surveillance.

Radiation doi: 10.3390/radiation6010010

Authors: David Macias-Verde Javier Burgos-Burgos Pedro C. Lara

Introduction: Lattice Radiation Therapy (LRT) is an evolving spatially fractionated radiation therapy (SFRT) technique that delivers heterogeneous dose distributions to large and radioresistant tumors. The literature highlights LRT’s potential for effective tumor debulking, palliation, and immune modulation. Effective LRT planning is crucial for maximizing tumor control while minimizing toxicity to organs at risk (OARs). The process involves defining the size, spacing, and arrangement of high-dose vortexes within the GTV. Traditionally, this has been a manual and time-consuming process, prone to inter-planner variability in vortex placement. Recent research has focused on developing automated or semi-automated tools to address these challenges, enhancing planning standardization. We aimed to systematically review for the first time the available scientific evidence of automated planning tools of vortexes for Lattice Radiotherapy and to assess the efficacy of such tools for standardizing Lattice Radiotherapy delivery. Methods: A systematic review of available studies in PubMed, Web of Science, and Scopus, including the terms “Lattice radiation therapy and (automated or optimized)”. Only LRT clinical planning reports published in English and with access to the full accepted text were considered eligible. This study was conducted in accordance with the PRISMA guidelines and was registered on the PROSPERO platform (CRD420251108024). Results: A total of 82 articles were found. Twenty articles fulfilled all inclusion criteria. Automated treatment planning tools have significantly improved the efficiency, consistency, and scalability of LRT planning, addressing limitations of manual planning. In conclusion, LRT should be planned to use automated tools to improve wide clinical standardization and implementation.

Radiation doi: 10.3390/radiation6010009

Authors: Masakatsu Tano Kodai Sagehashi Koichi Chida

This retrospective study evaluated patient radiation dose during fluoroscopy-guided peripherally inserted central catheter (PICC) placement. A total of 1240 consecutive adult patients who underwent PICC placement between January 2023 and December 2024 were analyzed. Patient radiation dose indices, including air kerma (AK) and dose–area product (DAP), as well as fluoroscopy time and number of radiographic acquisitions, were obtained from the radiology information system. The mean and median AK were 2.47 mGy and 1.54 mGy, respectively, and the median DAP was 901.9 mGy·cm2. The median fluoroscopy time was 1.9 min, and the median number of radiographic acquisitions was 1. Patient radiation dose during PICC placement was lower than the Japanese Diagnostic Reference Levels (Japan DRLs 2025). AK showed a strong positive correlation with fluoroscopy time (Spearman’s rank correlation, ρ = 0.77), whereas correlations between AK and BMI or the number of radiographic acquisitions were weak. In some patients with high BMI, AK values exceeding 40 mGy were observed. These findings indicate that patient radiation dose during PICC placement is generally low but remains closely associated with fluoroscopy time. Optimization of the patient radiation dose should be considered, particularly for patients with high BMIs or those undergoing repeated PICC placements.

Radiation doi: 10.3390/radiation6010008

Authors: Victor C. Ng Jill Steele Edward Soffen

Stereotactic body radiation therapy (SBRT) for localized prostate cancer delivers high doses per fraction, making dose constraints for the rectum and other organs at risk critical during treatment planning. This study evaluated the association between prostate–rectum separation, achieved with a biodegradable balloon rectal spacer at different anatomical levels, and corresponding organ-at-risk dose patterns. Thirty-three patients underwent transperineal balloon spacer implantation followed by SBRT to 36.25 Gy in five fractions. Prostate–rectum separation at the apex, mid-gland, and base were measured on CT and/or MRI and categorized as <10 mm, 10–14 mm, or ≥14 mm. Rectal dose–volume parameters and mean doses to the rectum, bladder, and penile bulb were assessed using linear regression analyses and group comparisons at 14 mm separation. Mean prostate–rectum separation was 16.6 mm overall, with minimal high-dose rectal exposure observed. Increasing separation was associated with reduced rectal dose–volume parameters at the apex and mid-gland, while greater base separation corresponded primarily to lower bladder mean dose. Increased apical separation was also associated with reduced penile bulb mean dose. No acute gastrointestinal toxicity was observed, and genitourinary toxicity was limited to low-grade events. These findings indicate that prostate–rectum separation varies by anatomical level and is associated with distinct organ-at-risk dose relationships in prostate SBRT.

Radiation doi: 10.3390/radiation6010007

Authors: Spyridon Zonitsas Angeliki Gkikoudi Kalliopi Kaperoni Sotiria Triantopoulou Panagiotis G. Matsades Despoina Diamantaki Athanasia Adamopoulou Ioannis Pantalos Constantinos Koumenis Michail Axiotis Anastasios Lagoyannis Georgia I. Terzoudi Michael Kokkoris Alexandros G. Georgakilas

Proton therapy offers superior dose localization, yet the biological effects of low-energy protons relevant to superficial tissues remain underexplored. We report the design and validation of a proton irradiation setup developed at the Tandem Accelerator of NCSR “Demokritos” for controlled radiobiological experiments. Monte Carlo simulations using Geant4 and Monte Carlo Damage Simulation (MCDS—Monte Carlo Damage Simulation) were used to determine proton energy spectra, linear energy transfer (LET), and predicted DNA damage yields. A single layer (15–20 μm in thickness) of human keratinocytes (HaCaT) was irradiated at doses from 0.65 to 3.65 Gy, and γ-H2AX foci were quantified as markers of tracks including one or more DNA double-strand breaks. The system achieved a uniform dose rate of 0.37 Gy/min, as calculated with Geant4, with a mean proton energy of 4.1 MeV (LET ≈ 8 keV/μm). A strong correlation (R2 = 0.93) was observed between proton dose and γH2AX foci per nucleus (~10 foci/Gy), reflecting damage-inducing proton tracks rather than individual DNA double-strand breaks. At higher doses, an increased fraction of cells exhibited pan-nuclear γH2AX staining, characterized by a diffuse γH2AX signal throughout the nucleus and commonly associated with extensive or clustered DNA damage and global chromatin phosphorylation. These responses are consistent with the well-established dense ionization patterns produced by low-energy protons, as indicated by the LET spectrum and supported by MCDS-predicted clustered damage yields. While the γH2AX assay does not directly resolve simple versus complex DNA lesions, the agreement between Monte Carlo modeling and the observed cellular stress responses indicates that the irradiation platform reliably reproduces the expected biological signatures of low-energy proton exposure. Consequently, the developed system provides a robust experimental tool for systematic investigations of cellular radiosensitivity and radiotoxicity, with potential applications in skin dosimetry and radioprotection.

Radiation doi: 10.3390/radiation6010006

Authors: Ali Nazarizadeh Quy Van-Chanh Le Wendy Phillips Tyron Turnbull Hien Le Chris Brown Ivan Kempson

Anesthesia is the gold standard for immobilization of tumor-bearing mice before radiotherapy which potentially induces stress and distorts disease progression. Irradiation of preclinical cancer models with clinical MV linear accelerator (LINAC) beams can benefit the translation of new strategies in radiation oncology. However, logistical constraints prohibit widespread use of clinical facilities. Currently, there is no detailed protocol on how to safely introduce mice to a clinical environment to be intervened on using hospital equipment. Here, a facile and high-throughput handling method is described that eliminates anesthesia and enables fractionated radiotherapy of multiple mice simultaneously for high-throughput studies. Subcutaneous breast tumor-bearing BALB/c mice were restrained in plastic restraint cones within a containment tray and received four fractions of 4 Gy X-rays from a 6 MV LINAC source over two weeks (two fractions/week). Both short- and long-term follow-up revealed no identifiable health issues or complications associated with the restraint procedure or radiation exposure in terms of body weight loss, skin burns or body condition scores. This method not only benefits animal welfare but also data quality by reducing stress/discomfort levels and confounding effects of anesthetics. It can be applied to a broader range of studies where mice need to be immobilized before intervention.

Radiation doi: 10.3390/radiation6010005

Authors: Anthony Kim Aliaksandr Karotki

Background: One method for the radiation therapy of rectal cancer is to set patients supine and treat them with volumetric modulated arc therapy (VMAT). The posterior skin dose is of concern due to undesirable bolusing from mounting surfaces the patient lays upon, namely the carbon fiber couch (CFC). The posterior skin dose may be mitigated by positioning the patient on top of a low-density material that separates the patient from the CFC. Purpose: Our objective was to determine the reduction in the posterior surface dose when a mattress or foam board is used to prop the patient away from the CFC. Materials and Methods: Three clinical rectal cancer patient VMAT plans were selected. A solid water phantom with optically stimulated luminescence dosimeters (OSLDs) placed at the posterior surface was mounted using three setups: directly on the CFC, with a mattress on the CFC, and with a 10 cm thick foam board on the CFC. The three VMAT plans were delivered to this phantom, with OSLDs measuring the posterior surface dose with each setup. In the treatment planning system (TPS), the CFC only, mattress, and foam board setups were simulated on the patient’s anatomy with posterior surface doses reported. Results: The OSLD measurements in the phantom showed that the mattress reduced the posterior surface dose on average by 1.3%, and the foam board reduced the dose by 8.3%. The TPS estimates demonstrated that, on average, the mattress reduced the surface dose by 15.8%, and the foam board reduced the dose by 33.0%. It is likely that the TPS had limitations accurately modeling the surface dose, so OSLD measurements were closer to clinical reality. Conclusions: The mattress does not reduce the posterior skin dose enough to warrant its use as a skin sparing device. The CFC produces a bolusing effect that can be reduced by separating the patient from the CFC with a 10 cm thick foam board.

Radiation doi: 10.3390/radiation6010004

Authors: Martine Rustøen Skregelid Kasim Ibrahim-Pur Flemming Skjøth Malene Roland Vils Pedersen Helle Precht

Background: Interpretation of radiographs is prone to diagnostic errors. Artificial intelligence (AI) has shown promising results in fracture detection, although systematic evaluation of software updates remains limited. This study compares the diagnostic performance of two versions of an AI-based fracture detection software in hand and ankle radiographs and assesses the influence of AI output on diagnostic decisions. Methods: This retrospective diagnostic accuracy study included 193 hand and ankle examinations obtained during routine clinical practice at Lillebaelt Hospital, Denmark. Radiographs were analysed using two versions of the same AI software and compared with the diagnostic report as the reference standard. Diagnostic performance of both versions was assessed using diagnostic accuracy metrics. Exploratory subgroup analyses were conducted to further investigate the difference in performance. The influence of AI was evaluated by the proportion of reports revised after review of AI output. Results: The newest software version demonstrated higher diagnostic performance than the older one (accuracy 0.933 vs. 0.824; p < 0.001). Similar improvements were observed across patient subgroups. Excluding radiographs containing casts resulted in only minimal changes in performance (accuracy in version 2: 0.930 vs. 0.933). In 8 of 15 discordant cases, reporting radiographers revised the initial assessment upon reassessment. Conclusions: The newest version demonstrated higher overall diagnostic performance, indicating that software updates can enhance the accuracy of AI-assisted fracture detection. The proportion of revised assessments suggests that radiographers’ decisions may be influenced by AI output.

Radiation doi: 10.3390/radiation6010003

Authors: Rami R. Abu-Aita M. C. Schell Kevin J. Parker

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. Pulmonary function tests (PFTs) and quantitative indices (QIs) of computed tomography (CT) are typically used to diagnose COPD. The purpose of this work was to determine the correlation of the vector divergence operator with PFTs and QIs in COPD patients and compare the divergence of normal lung function to that in COPD. Vector divergence is computed for 73 patients with four-dimensional CT scans retrospectively identified as normal (n = 37) and COPD (n = 36), which includes emphysema (n = 13). The divergence is the flux per unit volume at a point in a vector field and reflects the local lung tissue expansion when the data are taken during inspiration. The divergence measures are strongly correlated with both PFTs and QIs of COPD patients and therefore are a useful biomarker in analyzing regional lung function. In physical terms, the divergence shows that there is a significant difference in lung tissue expansion between normal subjects and patients with airflow obstruction as in emphysema and COPD. The divergence analysis also enables new images using color overlays to provide a functional measure (local expansion capability) to the anatomical CT image.

Radiation doi: 10.3390/radiation6010002

Authors: Peter du Plessis Pauline Busisiwe Nkosi Shankari Nair John Akudugu

Breast cancer remains a major global health challenge, with treatment access further constrained during the COVID-19 pandemic, particularly in resource-limited settings. This study evaluates the in vitro effects of hypofractionated versus conventionally fractionated radiotherapy on three breast cell lines: MCF-7 (oestrogen receptor-positive, ER+/PR+), MDA-MB-231 (triple-negative: ER−/PR−/HER2−), and MCF-10A (non-tumorigenic mammary epithelial). Cells were exposed to cobalt-60 γ-rays, and radiobiological endpoints assessed included clonogenic survival, α/β ratios, adaptive responses, migration, invasion, and cytotoxicity through lactate dehydrogenase assays. The α/β ratios ranged from 2.5 to 5.4 Gy across breast cancer subtypes. Hypofractionation reduced survival in hormone receptor-positive cells, whereas triple-negative cells exhibited increased survival. Adaptive radiation responses enhanced viability across all cell lines, while non-cancerous MCF-10A cells demonstrated reduced migration following treatment. These findings suggest that hypofractionated radiotherapy may be beneficial in hormone receptor-positive breast cancer, while triple-negative disease may show a trend toward different responses, although this was not statistically significant (MDA-MB-231, p = 0.290). The results underscore the importance of tailoring fractionation strategies to breast cancer subtype and highlight the translational potential of preclinical radiobiology in guiding personalised radiation oncology approaches.

Radiation doi: 10.3390/radiation6010001

Authors: Ryutaro Mori Koichi Okuda Tomoya Okamoto Yoshihisa Niioka Kazuya Tsushima Masakatsu Tsurugaya Shota Hosokawa Yasuyuki Takahashi

We compared scatter correction (SC) in single-photon emission computed tomography (SPECT) images using effective scatter source estimation (ESSE) and the triple-energy window (TEW) method. We acquired 99mTc and 123I images of brain, myocardial, and performance phantoms containing rods with different diameters. We assessed contrast ratios (CRs) and ROI-based noise metrics (coefficient of variation, signal-to-noise ratio, and contrast-to-noise ratio [CNR] ). Under 99mTc, ESSE yielded higher CRs than TEW across all phantoms (mean difference 0.04, range 0.01–0.05) and produced the highest CNR in the myocardial phantom, improving the conspicuousness of the simulated defect. Under 123I, CR differences between ESSE and TEW were small and inconsistent (performance phantom: −0.04 to 0.06; brain phantom: −0.01 to 0.00). A Monte Carlo simulation (point source in air) showed substantial photopeak window penetration for cardiac high-resolution collimators (40.0%) but low penetration for medium-energy general-purpose collimators (5.1%), supporting photopeak contamination as a contributor to the 123I findings and potentially attenuating the apparent advantage of model-based SC that does not explicitly account for penetration photons. These findings suggest that SC selection should consider the radionuclide and imaging target and that ESSE might be a reasonable option for 99mTc myocardial imaging under the settings examined.

Radiation doi: 10.3390/radiation5040039

Authors: Cynthia Lilieholm Jen Zaborek Ohyun Kwon Adedamola O. Adeniyi Caroline P. Kerr Hansel Comas Rojas Malick Bio Idrissou Carolina A. Ferreira Paul A. Clark Won Jong Jin Joseph J. Grudzinski Amy K. Erbe Eduardo Aluicio-Sarduy Thines Kanagasundaram Justin J. Wilson Jonathan W. Engle Reinier Hernandez Bryan Bednarz Zachary S. Morris Jamey P. Weichert

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.

Radiation doi: 10.3390/radiation5040038

Authors: Caroline Hircock Adrian Wai Chan Anh Hoang Hanbo Chen Merrylee McGuffin Danny Vesprini Liying Zhang Matt Wronski Irene Karam

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.

Radiation doi: 10.3390/radiation5040037

Authors: Jacopo Giuliani Daniela Mangiola Giuseppe Napoli Maria Viviana Candela Teodoro Sava Francesco Fiorica

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.

Radiation doi: 10.3390/radiation5040036

Authors: Ezek Mathew Reyhan Meetheen Anand Shivnani Rob Dickerman

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.

Radiation doi: 10.3390/radiation5040035

Authors: Shayenthiran Sreetharan Sujeenthar Tharmalingam Cameron Hourtovenko Felix Tubin Christopher D. McTiernan Christopher Thome Neelam Khaper Douglas R. Boreham Simon J. Lees T.C. Tai

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.

Radiation doi: 10.3390/radiation5040034

Authors: Damir Vučinić Matea Lekić Mihaela Mlinarić Giovanni Ursi Nikola Šegedin Vanda Leipold Domagoj Kosmina Hrvoje Kaučić Karla Schwarz Dragan Schwarz

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.

Radiation doi: 10.3390/radiation5040033

Authors: Banghao Zhou Lixiang Guo Weiguo Lu Mahbubur Rahman Rongxiao Zhang Varghese Anto Chirayath Yang Kyun Park Strahinja Stojadinovic Marvin Garza Ken Kang-Hsin Wang

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.

Radiation doi: 10.3390/radiation5040032

Authors: Mostafa Zahed Maryam Skafyan

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 64×64 textured ROIs discretized to Ng=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×(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 |r|≈0.98; and Lac versus GLCM inverse difference normalized (IDN), a homogeneity measure that weights small intensity differences more heavily, with |r|≈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.

Radiation doi: 10.3390/radiation5040031

Authors: Hyeon Yu

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.

Radiation doi: 10.3390/radiation5040030

Authors: Xin Meng Leah Nemzow Yaru Han Kechun Wen Sally A. Amundson Helen C. Turner Qiao Lin

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.

Radiation doi: 10.3390/radiation5040029

Authors: Papichaya Yudech Wisawa Phongprapun Pittaya Dankulchai Duangporn Polpanich Abdelhamid Elaissari Rujira Wanotayan Kulachart Jangpatarapongsa

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.

Radiation doi: 10.3390/radiation5040028

Authors: Zuhair Zaidi Sarah Attia Muaz Wahid Yin Xi Hareena Sangha Kelly Scott Rupali Kumar Flavio Duarte Silva Avneesh Chhabra

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.

Radiation doi: 10.3390/radiation5040027

Authors: Aliyu Yakubu Ibrahim Abdulazeez Okene Chinedu Amaeze Frank Maruf Lawal Shamsaldeen Ibrahim Saeed Mohammed Dauda Goni

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.

Radiation doi: 10.3390/radiation5030026

Authors: Gal Feller Duvern Ramiah Faiza Mahomed Liviu Feller Razia A. G. Khammissa

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.

Radiation doi: 10.3390/radiation5030025

Authors: Luca Cmelak Mohamed H. Khattab Anthony J. Cmelak

Osteoblastoma is a rare benign osteoid-producing tumor, accounting for about 1% of all primary bone neoplasms [...]

Radiation doi: 10.3390/radiation5030024

Authors: Daniel Banks Elise Kapshtica Jia Ali Sami Raja Madhesh Raja Mishka Ali Muhammad Maqbool

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 Zeff of tissues is observed because Zeff 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 Zeff/Aeff instead of just the effective charge number. This increase in the Compton mass attenuation coefficient with increasing Zeff/Aeff is rapid for the lower values of Zeff/Aeff. However, for a higher Zeff/Aeff 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.

Radiation doi: 10.3390/radiation5030023

Authors: Christoph Oehler Michel Eric Nicolas Zimmermann Mohsen Mousavi Kattic Ram Joorawon Marcel Blum Christian Herrmann Daniel Rudolf Zwahlen

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.

Radiation doi: 10.3390/radiation5030022

Authors: Miguel Felizardo Elisabete Dias

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.

Radiation doi: 10.3390/radiation5020021

Authors: Shannon Hartzell Keith M. Furutani Alessio Parisi Tatsuhiko Sato Yuki Kase Christian Deglow Thomas Friedrich Chris J. Beltran

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.

Radiation doi: 10.3390/radiation5020020

Authors: Hilke Vorwerk Gertrud Schmich Philipp Lishewski Sebastian Adeberg Ahmed Gawish

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.

Radiation doi: 10.3390/radiation5020019

Authors: Leonie Eastlake Prakash Thanikachalam David Cameron Dimitri Dimitroyannis Wanda Ingham Pascoe Mannion Gillian Clarkson Aashish Vyas Anthony Chalmers Dennis Hadjiyiannakis

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.

Radiation doi: 10.3390/radiation5020018

Authors: Ryosuke Ogasawara Akiko Irikawa Yuya Watanabe Tomoya Harada Shota Hosokawa Kazuya Koyama Keisuke Tsuda Toru Kimura Koichi Okuda Yasuyuki Takahashi

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 (N10mm), % contrast-to-% background variability ratio (QH10mm/N10mm), 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.

Radiation doi: 10.3390/radiation5020017

Authors: Lisa Bauer Bayan Alkotub Markus Ballmann Khouloud Hachani Mengyao Jin Morteza Hasanzadeh Kafshgari Gerhard Rammes Alan Graham Pockley Gabriele Multhoff

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.

Radiation doi: 10.3390/radiation5020016

Authors: Manuel Higueras Hans Carrillo

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.

Radiation doi: 10.3390/radiation5020015

Authors: Nancy Huang Joseph Descallar Wei Chua Weng Ng Emilia Ip Christopher Henderson Tara L. Roberts Stephanie Hui-Su Lim

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.

Radiation doi: 10.3390/radiation5020014

Authors: Lena Blanke Laura S. Hildebrand Rainer Fietkau Luitpold Distel

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.

Radiation doi: 10.3390/radiation5020013

Authors: Isabelle F. Vanhaezebrouck R. Timothy Bentley Alex Georgiades Susan Arnold Joshua A. Young Nathan Claus Laura Danaher Joshua B. Klutzke Matthew L. Scarpelli

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.

Radiation doi: 10.3390/radiation5020012

Authors: Radiation Editorial Office Radiation Editorial Office

Radiation’s Editorial Office wishes to make the following changes to the published article [...]

Radiation doi: 10.3390/radiation5020011

Authors: Mateusz Bielecki Khadijeh Saednia Fang-I Lu Shely Kagan Danny Vesprini Katarzyna J. Jerzak Roberto Salgado Raffi Karshafian William T. Tran

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.

Radiation doi: 10.3390/radiation5020010

Authors: Ines Delfino Maria Daniela Falco Maria Lepore M. Portaccio

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.

Radiation doi: 10.3390/radiation5010009

Authors: Yawo Atsu Constantino Fiagan Kodjo Joël Fabrice N‘Guessan Adama Diakité Komlanvi Victor Adjenou Thierry Gevaert Dirk Verellen

Background: Quality assurance (QA) programs are designed to improve the quality and safety of radiation treatments, including patient-specific QA (PSQA). The objective of this study was to investigate the conditions in which pretreatment PSQA is performed, to evaluate the root cause of the implementation of more complex techniques, and to identify areas for potential improvement. Materials/Methods: The Octavius 4D (O4D) system accuracy was evaluated using an O4D homogeneous phantom for different field sizes. Tests of the system response to dose linearity, field sizes, and PDD differences were performed against calculated doses for a 6 MV photon beam. The pretreatment verification of 40 VMAT plans was performed using the PTW VeriSoft software (version 8.0.1) for local and global 3D gamma analysis. The reconstructed 3D dose was compared to the calculated dose using 2%/2 mm and 3%/3 mm, 20% of the low-dose threshold, and 95% of the gamma passing rate (%GP) tolerance level. The sensitivity of the O4D system in detecting VMAT delivery and setup errors has been investigated by measuring the variation in %GP values before and after the simulated errors. Results: The O4D system reported good agreement for linearity, field size, and PDD differences with TPS dose, being within ±2% tolerance. The output factors were consistent between the ionization chamber and the O4D detector down to a 4 × 4 cm2 field size with a maximum deviation less than 1%. The introduction of deliberate errors caused a decrease in %GP values. In most scenarios, the %GP value of the simulated errors was detected with 2%/2 mm. Conclusion: The results indicate that the O4D system is sensitive enough to detect delivery and setup errors with the restrictive global criterion of 2%/2 mm for routine pretreatment verification.

Radiation doi: 10.3390/radiation5010008

Authors: Chunming Gu Robert F. Hobbs Ana P. Kiess Junghoon Lee Todd McNutt Harry Quon Zhuoyao Xin Tahir I. Yusufaly

Salivary glands are common organs at risk in both head and neck external beam radiotherapy (EBRT) and radiopharmaceutical therapy (RPT), but incidences of xerostomia in RPT are inconsistent with the EBRT Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) limits. In EBRT, salivary glands are usually assumed to be parallel organs, with QUANTEC guidelines based on Dmean, but this is known to be a gross over-simplification of the full complexity of the underlying functional organization. The goal of this work is to combine machine learning of EBRT dose–outcome data with stylized small-scale RPT dosimetry to discover more reliable normal tissue complication probability (NTCP) models of xerostomia across both modalities. A retrospective cohort of 211 EBRT patients was analyzed using a custom-designed in-house machine learning workflow. From this, a hierarchy of three models of increasing complexity was trained, evaluated for performance and generalization, and coupled with stylized small-scale salivary gland dosimetry to assess the influence of model complexity on the predicted NTCP for plausible patterns of RPT dose nonuniformity. The three models in the hierarchy (A, B, C), in increasing order of complexity, associate xerostomia with the following: the mean dose to the whole contralateral parotid (model A), the mean dose to a ductally localized region (model B) and a serial interaction dose term between two ductal sub-compartments (model C). While the difference between the three models for EBRT p-values and AUCs is rather marginal, for physiologically driven ductal dose distributions in RPT, the predicted reduction in TD50 can be as large as a factor of 10. These results provide hints towards a plausible reconciliation of the observed inconsistency of xerostomia in RPT with EBRT dose limits.

Radiation doi: 10.3390/radiation5010007

Authors: Cuiping Yuan Jessica An Seyedmehdi Payabvash

Radiomics and deep learning computer vision algorithms can extract clinically relevant information from medical images, providing valuable insights for accurate diagnosis of cancerous lesions, tumor differentiation and molecular subtyping, prediction of treatment response, and prognostication of long-term outcomes. In head and neck squamous cell carcinoma (HNSCC), growing evidence supports the potential role of radiomics and deep learning models in predicting treatment response, long-term outcomes, and treatment complications following radiation therapy. This is especially important given the pivotal role of radiotherapy in early-stage and locally advanced HNSCC, as well as in post-operative and concomitant chemoradiotherapy. In this article, we summarize recent studies highlighting the role of radiomics in predicting early post-radiotherapy response, locoregional recurrence, survival outcomes, and treatment-related complications. Radiomics-guided tools have the potential to personalize HNSCC radiation treatment by identifying low-risk patients who may benefit from de-intensified therapy and high-risk individuals who require more aggressive treatment strategies.

Radiation doi: 10.3390/radiation5010006

Authors: Payton H. Stone Lam M. Lay Raymi Ramirez Daniel Neck Connel Chu Joyoni Dey David Solis

Effective dose calculation is essential for optimizing Gamma Knife (GK) stereotactic radiosurgery (SRS) treatment plans. Modern GK systems allow independent sector activation, enabling complex dose distributions per shot. This study presents a dose approximation method designed to account for shot flexibility and generate 3D doses external to GammaPlan. A treatment plan was created with the TMR10 calculation for individual sector activations using a Radiosurgery Head Phantom. The resulting dose arrays established a basis set of sector-specific distributions, which were then referenced by shot parameters from the plan, allowing dose accumulation through superposition. This superposition approximation (SA) was compared to the original TMR10 using the Dice Similarity Coefficient (DSC), 95% Hausdorff Distance (HD95), and GK deliverability metrics: coverage, selectivity, and gradient index, across an isodose normalization range from 10% to 90%. In a cohort of 30 patients with 71 targets, strong agreement was observed between TMR10 and SA in the clinically used 50–60% isodose range, with DSC above 85% and HD95 under 2.18 mm. The average differences for the coverage, selectivity, and gradient index were 0.014, 0.008, and 0.118, respectively. This method accurately approximates TMR10 calculations within clinically relevant ranges, offering an external tool to assess 3D dose distributions for GK treatment plans.

Radiation doi: 10.3390/radiation5010005

Authors: Ryosuke Miki Tatsuya Tsuchitani Yoshiyuki Takahashi Kazuhiro Kitajima Yasuyuki Takahashi

The image quality index for whole-body bone scintigraphy has traditionally relied on the total count (Total-C) with a threshold of ≥1.5 million counts (MC). However, Total-C measurements are susceptible to variability owing to urine retention. This study aimed to develop a skeletal count (Skel-C)-based index, focusing exclusively on bone regions, to improve the accuracy of image analysis in bone scintigraphy. To determine the optimal Skel-C-based threshold, Skel-C thresholds were set at 0.9, 1.0, 1.1, and 1.2 MC, and Total-C thresholds were set at 1.75, 2.0, and 2.25 MC. Patients were then categorized based on whether their values were above or below these thresholds. The group including all cases was defined as the Total-C 1.5 high group. Sensitivity and specificity were calculated for each group, and receiver operating characteristic analyses and statistical evaluations were conducted. The specificity of the bone scintigraphy image analysis program in the Skel-C < 0.9 MC group was significantly lower than that in the Skel-C ≥ 0.9 MC and Total-C 1.5 high groups. The decrease in specificity was evident only with Skel-C and was not identified based on Total-C levels. These findings highlight the importance of achieving Skel-C ≥ 0.9 MC and suggest that Total-C alone is insufficient for reliable image assessment.

Radiation doi: 10.3390/radiation5010004

Authors: Alireza Omidi Elisabeth Weiss Mateb Al Khalifa Siyong Kim

Background: We aimed to measure the pacemaker- and defibrillator-induced distortion at 0.35T and 3.0T magnetic fields. Methods: The pacemaker/defibrillator was placed at the top center of a water-filled/MagPhan phantom, followed by a T1 scan at 3T and a TrueFISP scan at 0.35T. The extent of distortion (i.e., the distance from the device to the furthest signal loss/void/rings) in the water-filled phantom was measured in MIM. For geometrical distortion (i.e., dislocation of geometrical structures), the spheres in the MagPhan phantom were contoured and their distortion was calculated based on their manufacturing coordinate positions. Results: The maximum extent of distortion caused by the defibrillator was 18.8 cm at 0.35T and 5.8 cm at 3.0T. Similarly, the maximum extent of distortion caused by the pacemaker was 9.28 cm at 0.35T and 2.8 cm at 3.0T. Geometrical distortion measurements using the MagPhan phantom showed that the maximum distortion caused by the defibrillator was 12.8 mm at 0.35T and 13.2 mm at 3.0T. Likewise, the maximum distortion caused by the pacemaker was 8.7 mm at 0.35T and 6.0 mm at 3.0T. Conclusions: Defibrillators cause larger distortions/signal voids than pacemakers, and require careful consideration when performing MRI-based treatment planning. To minimize distortion, sequences with lower sensitivity to magnetic field inhomogeneity should be used.

Radiation doi: 10.3390/radiation5010003

Authors: Judith N. Rivera Keith Laemont Artak Tovmasyan Stefan Stryker Kenneth Young Theresa Charity Gregory M. Palmer Sha Chang

Spatially fractionated radiation therapy (SFRT) has a long history of treating bulky and hypoxic tumors. Recent evidence suggests that, compared to conventional uniform dose radiation therapy, SFRT may utilize different mechanisms of tumor cell killing, potentially including bystander and immune-activating effects. The abscopal effect in radiation therapy refers to the control or even elimination of distant untreated tumors following the treatment of a primary tumor with radiation, a process believed to be immune-mediated. Such effects have been shown to be enhanced by immunotherapy, particularly immune checkpoint inhibition. In this manuscript, we explore the potential synergy of spatially fractionated radiation therapy, in the form of kV x-ray minibeam, combined with PD-L1 checkpoint inhibition in a murine mammary carcinoma model at conventional dose-rate. We found that minibeam of peak/valley doses of 50 Gy/3.7 Gy performed statistically equivalent but trending better than that of 100 Gy/7.4 Gy in its abscopal effect and so 50 Gy/3.7 Gy was selected for further studies. Our findings indicate that the abscopal effect is significantly greater in the minibeam plus anti-PD-L1 treated animals compared to those receiving uniform dose radiation therapy plus anti-PD-L1 (p = 0.04948). Immune cell profiling in the minibeam plus anti-PD-L1 group compared to uniform dose reveals a consistent trend towards greater immune cell infiltration in the primary tumor, as well as a higher percentage of CD8+ T cells, both systemically and at the abscopal tumor site.

Radiation doi: 10.3390/radiation5010002

Authors: Alessio Parisi Keith M. Furutani Shannon Hartzell Chris J. Beltran

Ion radiotherapy requires accurate relative biological effectiveness (RBE) calculations to account for the markedly different biological effects of ions compared to photons. Microdosimetric RBE models rely on descriptions of the energy deposition at the microscopic scale, either through radial dose distributions (RDDs) or microdosimetric probability density distributions. While RDD approaches focus on the theoretical description of the energy deposition around the ion track, microdosimetric distributions offer the advantage of being experimentally measurable, which is crucial for quality assurance programs. As the results of microdosimetric RBE models depend on whether RDD or microdosimetric distributions are used, the model parameters are not interchangeable between these approaches. This study presents and validates a method to reproduce the published reference biological and clinical dose calculations at NIRS-QST for only carbon ion radiotherapy by using the modified microdosimetric kinetic model (MKM) alongside microdosimetric distributions instead of the reference RDD approach. To achieve this, Monte Carlo simulations were performed to estimate the variation of the radiation quality within and outside the field of pristine and spread-out Bragg peaks. By appropriately optimizing the modified MKM parameters for microdosimetric distributions assessed within water spheres, we successfully reproduced the results of calculations using the reference NIRS-QST RDD, generally within 2%.

Radiation doi: 10.3390/radiation5010001

Authors: Pilar Simmons Chase Swinton Simeon Simmons Taylor McElroy Antiño R Allen

The pursuit of exploring the outer space environment for biological research has been a topic of interest for nearly 60 years. The success of the next phase of space exploration depends on the ability to increase crew safety by identifying ways to mitigate these threats. Using a universal scientific citation indexing tool, we extracted data on literature production in terms of the most prolific key terms, authors, countries, institutions, and journals for two distinct topic sets related to space radiation research published from 1 January 1990 to 31 December 2023. The focus of space radiation research in relation to its effects on human health has fluctuated over time, as reflected in the term maps that were generated for each decade. Our bibliometric analysis provides insight into the trends in the top producers in the space radiation research field over the years, as well as into how the focus of such studies has evolved throughout the decades.

Radiation doi: 10.3390/radiation4040029

Authors: Peter du Plessis Pauline Busisiwe Nkosi Shankari Nair John Akudugu

The rising incidence of prostate cancer necessitates innovative treatment approaches, particularly as diseases such as the COVID-19 pandemic can disrupt traditional cancer care. This study aims to evaluate the impact of hypofractionated versus conventionally fractionated radiotherapy on prostate cancer cell lines in vitro. Prostate cancer cell lines (PC-3 and DU-145) were exposed to varying doses of radiation alongside non-cancerous BPH-1 cells. We assessed radiation effects on cell proliferation, viability, colony formation, DNA repair, migration, invasion, and cytotoxicity. The results demonstrated that the prostate cell lines exhibited varying responses, with hypofractionation favourably impacting aggressive PC-3 cells while preserving non-cancerous cells. In contrast, conventional fractionation led to increased invasion and cytotoxicity in both prostate cancerous cell lines. These findings advocate for personalised radiation therapy approaches that enhance treatment efficacy by considering the distinct behaviours of differing prostate cancer subtypes.

Radiation doi: 10.3390/radiation4040028

Authors: Carlos J. Roldan Thomas Chai Lei Feng Ian Huh Billy Huh

Background: Vertebral augmentation (VA) procedures are used to treat painful vertebral fractures caused by malignancies, but there are few data on the radiation exposure for patients and proceduralists during these VA procedures. We retrospectively examined the radiation dose exposure during VA procedures and defined the characteristics of patients who underwent such procedures. Methods: We conducted a retrospective observational cohort study including patients with cancer who experienced axial back pain from compression fractures caused by malignancies. Participants were identified using an electronic medical records database and must have had evidence of stable vertebral compression fractures upon imaging and documentation of a clinical evaluation. We collected data on patient demographics, fluoroscopy time (FT) and dose (FD) during the procedure, the volume of polymethylmethacrylate injected, and reported complications. Results: Overall, 140 patients were included. Their median age was 69, and they were mostly men (n = 79). The most common diagnosis was multiple myeloma (41.4%). Most patients had a single-level compression fracture of the thoracolumbar spine. The mean FT was 233.80 s, with higher FTs for patients with an elevated body mass index and patients younger than 60 years. The average FD was 157.98 mGy, with higher FDs for patients with an elevated BMI and for male patients. Pain relief was not associated with FT or FD. Conclusions: Patients with cancer who underwent VA experienced longer FT and higher FD compared to their non-cancer counterparts in the literature. However, we found multiple confounders for this relationship.

Radiation doi: 10.3390/radiation4040027

Authors: Shopnil Prasla Daniel Moore-Palhares Daniel Dicenzo LaurentiusOscar Osapoetra Archya Dasgupta Eric Leung Elizabeth Barnes Alexander Hwang Amandeep S. Taggar Gregory Jan Czarnota

The objective of this study was to evaluate the effectiveness of utilizing radiomic features from radiation planning computed tomography (CT) scans in predicting tumor progression among patients with cervical cancers. A retrospective analysis was conducted on individuals who underwent radiotherapy for cervical cancer between 2015 and 2020, utilizing an institutional database. Radiomic features, encompassing first-order statistical, morphological, Gray-Level Co-Occurrence Matrix (GLCM), Gray-Level Run Length Matrix (GLRLM), and Gray-Level Dependence Matrix (GLDM) features, were extracted from the primary cervical tumor on the CT scans. The study encompassed 112 CT scans from patients with varying stages of cervical cancer ((FIGO Staging of Cervical Cancer 2018): 24% at stage I, 47% at stage II, 21% at stage III, and 10% at stage IV). Of these, 31% (n = 35/112) exhibited tumor progression. Univariate feature analysis identified three morphological features that displayed statistically significant differences (p < 0.05) between patients with and without progression. Combining these features enabled a classification model to be developed with a mean sensitivity, specificity, accuracy, and AUC of 76.1% (CI 1.5%), 70.4% (CI 4.1%), 73.6% (CI 2.1%), and 0.794 (CI 0.029), respectively, employing nested ten-fold cross-validation. This research highlights the potential of CT radiomic models in predicting post-radiotherapy tumor progression, offering a promising approach for tailoring personalized treatment decisions in cervical cancer.

Radiation doi: 10.3390/radiation4040026

Authors: Luca Marinelli Sara Mercogliano Oscar Selvaggio Giuseppe Carrieri Raffaele Sorrentino Paola Mangano Gianluca Prencipe Luca Macarini Grazia Casavecchia Matteo Gravina

Background: To evaluate p-Cry in 10 years as a feasible and radical approach in patients with small renal masses (<5 cm), we evaluated technical success, side effects, and survival rates. Materials and Methods: We retrospectively evaluated 421 patients with small renal masses (<5 cm) with a median age of 70 years (47–92 C.I.) between June 2014 and July 2024 at our department. We also evaluated side effects, surgical radicality, and therapeutic outcomes of renal functions. Survivals were also evaluated in terms of disease-free, metastasis-free, and cancer-related survival rates. Results: Median follow-up was 90 months (1–120 months C.I.), and median size of the tumor was 3.85 cm (1–4 C.I.). Two cryoprobes were used in median, and two 10-min freeze–thaw cycles were performed. The technical efficacy rate was 100%, whereas only one of 121 lesions required retreatment. No impact on the renal function was registered after p-Cry. Cancer-free survival and metastases-free survival was reached. Conclusions: Compared to surgery, p-Cry is a feasible treatment option in patients with small renal masses, as it does not affect renal function and gives patients good survival rates.

Radiation doi: 10.3390/radiation4040025

Authors: Sandra Kumar Angelica Gonzalez David Farbo Karen Albritton Anish Ray

Although radiation therapy is the leading option for effective cancer treatment, a prevalent side effect associated with it is dermatitis. Despite some available literature on this topic, there remain many gaps that need to be addressed. The goal of this study is to determine the incidence of radiation-induced dermatitis (RID) among children receiving proton and photon therapies; a retrospective chart review, at a single institution, was conducted on oncology patients who underwent proton or photon therapy radiation between 2018 and 2023. Significant differences were found between the Radiation Therapy Oncology Group (RTOG) score and the total radiation dose (p = 0.04). The median total dose of radiation received by those with an RTOG score of l was 5040.0 mGy and increased to 7600 mGy for those with a score of 3. A significant association was found between those who received chemotherapy and dermatitis (p = 0.04). No significance was found between the incidence of dermatitis in photon and proton therapy (p = 1.00). The study showed that multiple factors, including total radiation dose and chemotherapy, can affect RID. These relationships can be used to determine the modality, dose, and additional treatment options best suited to treat cancer patients in the pediatric population.

Radiation doi: 10.3390/radiation4040024

Authors: Miwako Nomura Rumi Murata Line Brøndum Eva Ehrnrooth Brita S. Sørensen Michael R. Horsman

This study investigated the effect of combining radiation with an angiogenesis inhibitor and vascular disrupting agent on tumor response and systemic toxicity. CDF1 mice with 200 mm3 foot implanted C3H mammary carcinomas were treated with TNP-470 (100 mg/kg every second day for 2 weeks; s.c.) and combretastatin A-4 phosphate (CA4P; 1 × 250 mg/kg, i.p.). Radiation (230-kV X-rays) was locally administered to tumors of restrained non-anesthetized mice. Response was tumor growth delay and change in mouse body weight. Radiation induced changes in serum levels of 10 cytokines up to 72-h after irradiation were measured using a Luminex assay. The results showed that TNP-470 (100 mg/kg × 7) or CA4P (250 mg/kg × 1) significantly (Student’s t-test; p < 0.05) inhibited tumor growth; the greatest effect when these two drugs were combined. TNP-470 and CA4P, alone or together, also significantly enhanced tumor response to radiation. No systemic toxicity occurred with drugs administered alone or in combination, but toxicity was observed when TNP-470 was combined with radiation. Serum cytokine levels only showed a significant transient increase in IL-6 1-h after irradiating. In conclusion, combining different acting vascular targeting agents with radiation increased anti-tumor activity. However, this benefit may sometimes be associated with a radiation-induced inflammatory response increasing systemic toxicity.

Radiation doi: 10.3390/radiation4040023

Authors: Tusher- Al-Arafat Aihong Mao Takanori Katsube Bing Wang

Radiotherapy remains a cornerstone in cancer treatment, leveraging ionizing radiation to eradicate malignant cells. Its efficacy, however, is frequently challenged by the heterogeneous sensitivity of tumors and surrounding tissues to radiation. Therefore, understanding the molecular mechanisms underlying radiosensitivity is crucial for improving treatment outcomes. Among the myriad of molecular players involved, the tumor suppressor protein p53 stands out as a central regulator with significant implications for radiosensitivity. Known as the “guardian of the genome”, p53 plays a pivotal role in maintaining genomic stability and orchestrating cellular responses such as cell cycle arrest, DNA repair, apoptosis, and senescence in response to various stress signals, including radiation-induced DNA damage. Activation of p53 triggers the transcription of target genes involved in DNA repair pathways, such as p21, MDM2, and GADD45, facilitating the repair of radiation-induced DNA damage or the elimination of irreparably damaged cells. This, in turn, influences the overall radiosensitivity of tissues. Mutations in the TP53 gene, which encodes p53, are among the most frequent genetic alterations in human cancers. Loss or dysfunction of p53 can compromise the cellular response to radiation, leading to increased resistance to therapy and poorer clinical outcomes. Conversely, intact p53 function is associated with enhanced radiosensitivity due to its ability to promote cell cycle arrest and apoptosis in response to radiation-induced DNA damage. In conclusion, elucidating the molecular mechanisms by which p53 influences radiosensitivity is essential for advancing our understanding of the radiation response in cancer cells and developing more effective therapeutic approaches to cancer treatment. This review provides a comprehensive overview of the multifaceted role of p53 in modulating cellular responses to radiation, emphasizing its influence on radiosensitivity.

Radiation doi: 10.3390/radiation4030022

Authors: Jade F. Monaghan Hugh J. Byrne Fiona M. Lyng Aidan D. Meade

Vibrational spectroscopic techniques, such as Fourier transform infrared (FTIR) absorption and Raman spectroscopy (RS), offer unique and detailed biochemical fingerprints by detecting specific molecular vibrations within samples. These techniques provide profound insights into the molecular alterations induced by ionising radiation, which are both complex and multifaceted. This paper reviews the application of rapid and label-free vibrational spectroscopic methods for assessing biological radiation responses. These assessments span from early compartmentalised models such as DNA, lipid membranes, and vesicles to comprehensive evaluations in various living biological models, including tissues, cells, and organisms of diverse origins. The review also discusses future perspectives, highlighting how the field is overcoming methodological limitations. RS and FTIR have demonstrated significant potential in detecting radiation-induced biomolecular alternations, which may facilitate the identification of radiation exposure spectral biomarkers/profiles.

Radiation doi: 10.3390/radiation4030021

Authors: Toshioh Fujibuchi Hiroyuki Arakawa Choirul Anam

X-ray fluoroscopy causes relatively high radiation exposure to physicians, radiation professionals, and patients. Understanding the behavior of scattered radiation is crucial for reducing occupational exposure. We developed a system for estimating radiation exposure during fluoroscopy by monitoring the position of the physician using a depth camera for radiation protection education. The dose distribution of scattered radiation in an X-ray room was simulated using Monte Carlo code. The data were displayed using augmented reality markers, and the dose at each joint point location was estimated using body tracking. Additional functions were created, such as displaying arbitrary two-dimensional cross-sections. The system performance ranged from 9.0 to 11.0 FPS with or without motion and a protective apron. The estimated doses were 0.93 to 1.21 times the measured doses for all joint points, except for the chest and pelvis. The estimated doses for the chest and pelvis were lower than the measured dose, with the minimum values being 0.72 and 0.60 times lower for the chest and pelvis, respectively. The system provides valuable insight into the estimation of radiation dose at joint points based on the physician’s position and movements, the physician’s optimal fluoroscopy location, and warning of dangerous exposure doses.

Radiation doi: 10.3390/radiation4030020

Authors: Njenga R. Kamau Michael S. Petronek

Nanotechnology has provided considerable advancements in an array of disciplines. Recently, it has been shown that ferumoxytol, a magnetite (Fe3O4) nanoparticle, can be oxidized by ionizing radiation. Ferumoxytol nanoparticles have high stability, and thus can be hypothesized that they have dosimetric potential. In this study, it has been observed that xylenol orange, a colorimetric detector of Fe3+ used for conventional Fricke dosimetry, was not able to detect radiolytic changes in ferumoxtyol. Electron paramagnetic resonance (EPR) spectroscopy was more readily able to evaluate the oxidation of ferumoxytol. EPR spectroscopy revealed that oxidation of 500 nM ferumoxytol in H2O was linear up to 20 Gy. This concentration, however, was unable to estimate the delivered dose from a Small Animal Radiation Research Platform system, as a 6 Gy dose was estimated to be 1.37 Gy, which represents a 79.2% underestimation of the dose delivered. Thus, while the high stability of Fe3O4 nanoparticles is attractive for use in pre-clinical radiation dosimetry, further radiochemical evaluation may be required before considering them for this application.

Radiation doi: 10.3390/radiation4030019

Authors: Alexandra D. Dreyfuss John P. Navilio Neal Kim Andy Shim Paul B. Romesser Marsha Reyngold Michael J. Zelefsky Christopher H. Crane Carla Hajj

Background: Pelvic reirradiation of de novo rectal or anal cancer after prior prostate cancer RT poses a significant risk of urinary and rectal fistula. In this report we describe the use of a rectal spacer to improve dosimetry and reduce this risk. Methods: Patients undergoing anorectal radiotherapy (RT) after prior prostate RT who had a rectal spacer placed prior to RT were identified in a prospective database. Patient, disease, and treatment characteristics were collected for these patients. Survival data were calculated from the end of RT. Radiation was delivered with intensity-modulated radiation therapy (IMRT) or proton beam therapy (PBT) following rectal spacer placement. Results: Rectal spacer placement with hydrogel injected transperineally under transrectal ultrasound guidance was successful in all five patients. MR/CT simulation 1–2 weeks post-spacer placement and IMRT or PBT delivered to a dose of 36–50 Gy in 24–30 fractions once or twice daily were tolerated well by all patients. The V100% of the PTV ranged from 62–100% and mean rectal and bladder dose ranged from 39–46 Gy and 16–40 Gy, respectively. At the last follow-up, three patients were alive and without evidence of disease up to 48 months out from treatment. There were no acute or late grade 3 or higher toxicities observed, but acute grade 2 proctitis was observed in all patients. Conclusions: The use of a rectal spacer placement to improve dosimetry of IMRT and PBT after prior prostate RT is safe and feasible in appropriately selected anorectal cancer patients.

Radiation doi: 10.3390/radiation4030018

Authors: Carla Pisani Alessandra Gennari Alessandro Carriero Marco Krengli Pierfrancesco Franco

A 98-year-old patient with cognitive impairment and a history of squamous cell carcinoma of the nasal pyramid was referred to the radiation oncology department of our institution’s hospital given that surgery was not recommended. The lesion was sized 6 × 6 cm, ulcerated, and bleeding; was significantly impairing the patient’s health-related quality of life, causing pain; and was not responsive to analgesics, including opioids. The patient experienced deterioration of her general conditions, with a Karnofsky performance status of 40. A single radiotherapy (RT) fraction was delivered on a weekly basis for 3 weeks, up to a total dose of 21 Gy, using a VMAT technique (7 Gy/fraction). The patient was given three fractions of radiotherapy, during which she received continuous assistance due to episodes of mental disorientation and an altered sense of consciousness. One month after the conclusion of the treatment, the patient exhibited a nearly complete clinical response, with full pain relief and an improved health-related quality of life. This favourable clinical outcome was maintained for a period of four months following the conclusion of RT. A brief review was performed on the role of hypofractionated radiation therapy in elderly patients with locally advanced skin cancer of the head and neck region.

Radiation doi: 10.3390/radiation4030017

Authors: Udayan Srivastava Parham Pezeshk Avneesh Chhabra

Aim: To evaluate patient satisfaction outcomes with respect to pain, discomfort, and quality of life with hematology/oncology referrals undergoing CT-guided bone marrow biopsy and compare these scores with those of patients undergoing in-office biopsy. Methods: A retrospective chart review was performed over 2 years with all patients who underwent CT-guided bone marrow biopsy at our university set-up. Age, gender, BMI, radiation dose (CTDI/DLP), number of in-office biopsies, number of CT-guided biopsies, type/amount of moderate sedation used, technical and pathologic success rates, and complication rates were recorded. All patients who underwent both in-office and CT-guided biopsy were contacted by telephone to answer a brief survey regarding pain, discomfort, quality of life, and future preference with respect to each biopsy. Results: A total of 32 patients underwent CT-guided bone marrow biopsy. Moderate sedation was utilized for all CT patients, and 19 patients underwent both in-office and CT-guided biopsies. Upon surveying the 19 patients who underwent both kinds of biopsies, on a scale of 1–10 (10 = highest discomfort and highest pain), the patients on an average reported 7.8 for in-office vs. 2.1 for CT for the discomfort level (p < 0.001) and 7.9 vs. 1.7 for the pain (p < 0.001). The patients reported an average quality-of-life score of 82 (out of a scale of 100) after CT procedures and 53 for in-office (p < 0.001). All patients reported that they would prefer CT-guided procedures with sedation versus in-office procedures in the future. Conclusion: CT-guided bone marrow biopsy is the preferred and more comfortable procedure, especially in low-pain-tolerant patients, although it involves more cost, conscious sedation, and radiation exposure.

Radiation doi: 10.3390/radiation4030016

Authors: Nikolaos Voulgaris Hikari Nishimura Shingo Tamaki Sachie Kusaka Isao Murata

Current radiation dosimeters sometimes face accuracy limitations or provide only cumulative doses over long periods. To contribute to this area, we developed a portable monitor that measures the energy spectrum and dose of gamma rays in real time. To achieve this, we used an improved sequential Bayesian estimation algorithm. The dose rate was then derived from the energy spectrum by applying a flux-to-dose conversion coefficient. The monitor consists mainly of a CsI(Tl) scintillator and a multi-pixel photon counter (MPPC). In developing this device, we focused on striking a balance between measurement accuracy, ease of use, and portability. As an essential aspect of the research, we investigated the influence of the CsI(Tl) crystal size on the performance of the monitor to determine an optimal size. This was accomplished by calculating the detection efficiency and energy resolution through experimental measurements using standard gamma-ray sources and simulations using MCNP5. Within the scope of the research, detector response functions were created for each crystal size for an energy range of 10 keV to 3 MeV. Considering an optimal balance of detection efficiency and energy resolution alongside a compact size suitable for portable applications, the crystal measuring 2.6 × 2.6 × 1.3 cm3 was deemed preferable.

Radiation doi: 10.3390/radiation4020015

Authors: Aryan Safakish Amir Moslemi Daniel Moore-Palhares Lakshmanan Sannachi Ian Poon Irene Karam Andrew Bayley Ana Pejovic-Milic Gregory J. Czarnota

Background: Head and neck cancer treatment does not yield desired outcomes for all patients. This investigation aimed to explore the feasibility of predicting treatment outcomes from routine pre-treatment magnetic resonance images (MRIs). Radiomics features were “mined” and used to train machine learning (ML) classifiers to predict treatment outcomes. Moreover, iterative deep texture analysis (DTA) was explored to boost model performances. Methods: Radiomics features were determined from T1-weighted post-contrast MRIs of pathologically involved lymph node (LN) segmentations for n = 63 patients. SVM, k-NN, and FLD classifier models were trained, selecting for 1–10 features. The model with the top balanced accuracy was chosen for an iteration of DTA. New feature sets were used to retrain and test the ML. Radiomics features were explored for a total of three layers through two iterations of DTA. Results: Models proved useful in predicting treatment outcomes. The best model was a nine-feature multivariable k-NN model with a sensitivity (%Sn) of 93%, specificity (%Sp) of 74%, 86% accuracy (%Acc), and 86% precision (%Per). The best model for two of the three classifiers (k-NN and FLD) was trained using features from three layers. The performance of the average k-NN and FLD models trained with features was boosted significantly with the inclusion of deeper-layer features. Conclusions: Pre-treatment LN MRIs contain quantifiable texture information that can be used to train ML models to predict cancer treatment outcomes. Furthermore, DTA proved useful to boosting predictive models.

Radiation doi: 10.3390/radiation4020014

Authors: Hannah Maione Julianna Sienna Kara L Schnarr Elysia K Donovan

Purpose: Uterine carcinosarcomas are highly aggressive tumors of the endometrium and are associated with a poor prognosis. The optimal adjuvant treatment for both early and advanced-stage patients remains unclear. Methods: Cases of uterine carcinosarcoma were identified in our institution’s pathology database between 2000 and 2022. Kaplan–Meier estimates were calculated for the local and distant recurrence-free, disease-free and overall survival; hazard ratios were calculated using Cox proportional hazards modelling for independent prognostic factors including the stage and treatment. Results: A total of 48 patients were identified as having uterine carcinosarcoma, of whom 70.8% were surgically staged. In total, 43 patients had pelvic-confined disease, while five had positive omental or peritoneal biopsies at surgery. There were 10 pelvic (20.8%) and 19 (39.6%) distant recurrences. None of the patients with stage IA disease who received chemotherapy and brachytherapy experienced disease recurrence. The local recurrence-free survival was 54.95%, the distant recurrence-free survival was 44.7%, and the overall survival was 59.6% at 5 years. Local recurrence-free survival and overall survival were inversely associated with advanced-stage OR 1.23 (p = 0.005) and OR 1.28 (p = 0.017), respectively, and no chemotherapy was associated with OR 1.96 (p = 0.06) and OR 2.08 (p = 0.056), respectively. Conclusion: The local and distant recurrence rates were high for advanced=stage patients even when treated with aggressive adjuvant therapy regimens. Chemotherapy may improve recurrence and survival. Early-stage patients may perform well with vaginal vault brachytherapy and chemotherapy. Further prospective comparisons are required between sequential, sandwich, and concurrent approaches to chemotherapy and radiotherapy, to optimize outcomes in this high-risk population.

Radiation doi: 10.3390/radiation4020013

Authors: Luca Weninger Adriana Morana Youcef Ouerdane Emmanuel Marin Aziz Boukenter Sylvain Girard

The combination of an ultra-low-loss optical fiber sensitive to ionizing radiation and an optical time domain reflectometer (OTDR) is investigated to explore the feasibility of a single-ended distributed radiation detector. The peculiarity of the tested fiber resides in its regenerative high radiation-induced attenuation (RIA) response in the infrared spectrum (1310 nm), which returns to a low value once the irradiation has ended, combined to its sensitivity, highly increasing with the dose rate. In this work, only some sections of the fiber line were irradiated with 100 kV X-rays at room temperature, to prove the spatially resolved radiation detection capabilities of the system. The transient RIA response of the fiber was characterized at different pre-irradiation doses. A pre-irradiation treatment was shown to stabilize the optical fiber response, improving its RIA vs. dose rate linearity and repeatability. This improved response, in terms of radiation quantification, comes at the cost of a lower detection threshold. This work lays the bases for a distributed radiation detector, with some capabilities in dose rate evaluation.

Radiation doi: 10.3390/radiation4020012

Authors: Malin Druid Emman Shubbar Johan Spetz Toshima Z. Parris Britta Langen Charlotte Ytterbrink Evelin Berger Khalil Helou Eva Forssell-Aronsson

The physiological process of iodine uptake in the thyroid is used for 131I treatment of thyroid diseases. Children are more sensitive to radiation compared to adults and may react differently to 131I exposure. The aims of this study were to evaluate the effects on thyroid protein expression in young and adult rats one year after 131I injection and identify potential biomarkers related to 131I exposure, absorbed dose, and age. Twelve Sprague Dawley rats (young and adults) were i.v. injected with 50 kBq or 500 kBq 131I and killed twelve months later. Twelve untreated rats were used as age-matched controls. Quantitative proteomics, statistical analysis, and evaluation of biological effects were performed. The effects of irradiation were most prominent in young rats. Protein biomarker candidates were proposed related to age, absorbed dose, thyroid function, and cancer, and a panel was proposed for 131I exposure. In conclusion, the proteome of rat thyroid was differentially regulated twelve months after low-intermediate dose exposure to 131I in both young and adult rats. Several biomarker candidates are proposed for 131I exposure, age, and many of them are known to be related to thyroid function or thyroid cancer. Further research on human samples is needed for validation. Data are avaiable via ProteomeXchange with identifier PXD024786.

Radiation doi: 10.3390/radiation4020011

Authors: Daeun Sung Jessica A. Baumgartner Jonathan D. Tward

PET/CT scans are being used to assess patients who have experienced biochemical failure following surgery or radiation therapy for localized prostate cancer. We aimed to evaluate the language used in report impressions and to determine the level of confidence that radiologists have when reporting on lesions in various anatomic sites. Between 2015 and 2021, 295 F18-fluciclovine PET/CT scan reports were identified. Thirteen phrases commonly used by radiologists in the report impression section to describe a lesion of interest were identified and categorized into three confidence categories: definitive (positive and negative), likely (consistent with, most likely, favors, probable), and unsure (suspicious for, concerning for, non-specific, conspicuous, compatible with, borderline, unknown). The use of definitive language varied depending on the anatomic site, with the highest use in bone (87.1%) and the lowest use in the intact prostate (34.6%). In patients with a PSA < 0.5, there was the highest degree of definitive certainty (89.2%), whereas in patients with a PSA > 1, there was the least definitive certainty (66.2%). The language used in these reports has not been standardized, with definitive, likely, and unsure findings reported in 68.6%, 9.7%, and 21.7% of scans, respectively.

Radiation doi: 10.3390/radiation4020010

Authors: Hong Yuan Judith N. Rivera Jonathan E. Frank Jonathan Nagel Colette Shen Sha X. Chang

For patients with recurrent brain metastases, there is an urgent need for a more effective and less toxic treatment approach. Accumulating evidence has shown that spatially fractionated radiation therapy (SFRT) is able to provide a significantly higher therapeutic ratio with lower toxicity compared to conventional radiation using a uniform dose. The purpose of this study was to explore the potential low toxicity benefit of mini-beam radiotherapy (MBRT), a form of SFRT, for whole-brain re-irradiation in a healthy mouse model. Animals first received an initial 25 Gy of uniform whole-brain irradiation. Five weeks later, they were randomized into three groups to receive three different re-irradiation treatments as follows: (1) uniform irradiation at 25 Gy; (2) MBRT at a 25 Gy volume-averaged dose (106.1/8.8 Gy for peak/valley dose, 25 Gy-MBRT); and (3) MBRT at a 43 Gy volume-averaged dose (182.5/15.1 Gy for peak/valley dose, 43 Gy-MBRT). Animal survival and changes in body weight were monitored for signs of toxicity. Brains were harvested at 5 weeks after re-irradiation for histologic evaluation and immunostaining. The study showed that 25 Gy-MBRT resulted in significantly less body weight loss than 25 Gy uniform irradiation in whole-brain re-irradiation. Mice in the 25 Gy-MBRT group had a higher level of CD11b-stained microglia but also maintained more Ki67-stained proliferative progenitor cells in the brain compared to mice in the uniform irradiation group. However, the high-dose 43 Gy-MBRT group showed severe radiation toxicity compared to the low-dose 25 Gy-MBRT and uniform irradiation groups, indicating dose-dependent toxicity. Our study demonstrates that MBRT at an appropriate dose level has the potential to provide less toxic whole-brain re-irradiation. Future studies investigating the use of MBRT for brain metastases are warranted.

Radiation doi: 10.3390/radiation4020009

Authors: Emanuele Chioccola Mara Caroprese Christina A. Goodyear Angela Barillaro Caterina Oliviero Stefania Clemente Chiara Feoli Luigi Formisano Antonio Farella Laura Cella Manuel Conson Roberto Pacelli

Background: Stereotactic body radiotherapy (SBRT) targeted at metastatic sites of disease progression is emerging as a potential therapeutic approach for managing oligoprogressive prostate cancer. However, a definitive benefit has yet to be demonstrated. Herein, we present our institution’s experience with this treatment approach. Methods: From April 2018 to March 2023, 11 patients affected by oligoprogressive prostate cancer were treated with SBRT targeting the nodal or bone sites of progression while maintaining the ongoing systemic therapy. Three patients were undergoing single-agent ADT (Androgen Deprivation Therapy), while the remaining eight were receiving a subsequent line of systemic therapy. All patients were evaluated with a pre-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT, which demonstrated between one and five localizations of disease. All the active sites were treated with SBRT in one (15–24 Gy) or three (21–27 Gy) fractions, except for one patient, who was treated in five fractions (35 Gy). PSA serum levels were tested at baseline, one month after RT and at least every three months; all patients underwent a post-treatment 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. The evaluated endpoints were PSA response, defined as a post-treatment decrease >50% from baseline measured within 6 months, time to next-line systemic treatment (NEST), local control (LC), biochemical progression-free survival (bPFS), radiological progression-free survival (rPFS) and freedom from polymetastatic progression (FPP). Results: Nineteen lesions were treated (seven nodal and twelve bone). At a median follow-up of 19 months (7–63), 9 of the 11 patients had a PSA response; all patients had local control of the treated metastases. A total of six patients switched to a next-line systemic treatment, with a median NEST of 13 months. Six patients had polymetastatic progression with an FPP median time of 19 months. No patients died during the follow-up period. The SBRT-related toxicity was negligible. Conclusions: Our data support the use of SBRT targeting the sites of oligoprogressive disease before moving to a subsequent line of systemic treatment in patients with metastatic prostate cancer. Prospective studies to evaluate the potential impact of this approach on overall survival are warranted.

Radiation doi: 10.3390/radiation4010008

Authors: Alireza Mortazavi Helia Yarbaksh Batool Faegheh Bahaaddini Baigy Zarandi Reza Yarbakhsh Fatemeh Ghadimi-Moghaddam Syed Mohammad Javad Mortazavi Masoud Haghani Donya Firoozi Lembit Sihver

Space exploration introduces astronauts to challenges, such as space radiation and microgravity. Researchers have investigated vitamin C as a potential radiation mitigator, as well as antioxidants for sustaining astronaut health. Our own studies demonstrate vitamin C’s life-saving radioprotective effects and its potential as a radiation mitigator, thus highlighting promise, even when administered 24 h post-exposure. This is particularly relevant in scenarios where astronauts may be exposed to sudden large solar particle events, potentially resulting in lethal doses of space radiation. The success of vegetable cultivation on the International Space Station using NASA’s Veggie system offers fresh, vitamin C-rich food. While approved supplements address somatic function, further research is needed to optimize vitamin C’s efficacy in humans, and to develop appropriate antioxidant cocktails for space missions. The variable vitamin C content in vegetables underscores the necessity for the utilization of artificial intelligence (AI) to assist astronauts in selecting and cultivating the vitamin C-rich vegetables best-suited to combat high levels of space radiation and microgravity. Particularly, AI algorithms can be utilized to analyze various factors, such as nutritional content, growth patterns, and cultivation methods. In conclusion, vitamin C shows significant potential for mitigating space radiation, and ongoing research aims to enhance astronaut health through optimal dietary strategies.

Radiation doi: 10.3390/radiation4010007

Authors: Mulugeta S. Goangul Daniel B. Erenso Ying Gao Li Chen Kwame O. Eshun Gisela Alvarez Horace T. Crogman

Background: Our study aimed to assess the radiation sensitivity of BT20, a human breast tumor cell line, using the laser-trapping technique and compare it with N2a and 4T1 cells. Additionally, we investigated the impact of the antitumor compound 2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) on radiation sensitivity. Methods and Materials: We employed laser trapping to calculate both the threshold ionization energy (TIE) and threshold radiation dose (TRD) for BT20, N2a, and 4T1 cells. We assessed the effect of DMDD on BT20 cells’ radiosensitivity and conducted comparisons across these cell lines. Results: Our findings reveal that DMDD significantly enhances the radiosensitivity of BT20 breast carcinoma cells. Moreover, we observed distinct trends in TIE and TRD across the three cell lines, with differences attributed to variations in cell size and composition. When multiple cell ionizations were considered, a notable reduction in TRD was observed, implicating factors such as the chain effect of ionizing radiation and the influence of DMDD. The study found that TIE increased with the number of cells in the trap while TRD consistently decreased across all three cell lines, suggesting comparable radiation sensitivity, and oligostilbene treatment further reduced TRD, presenting the potential for enhancing therapeutic ratios in cancer treatment. Conclusion: The antitumor compound DMDD enhances the radiosensitivity of BT20 breast carcinoma cells, highlighting its potential in cancer treatment. Furthermore, our study underscores the impact of cell size and multiple-cell ionizations on TRD. Leveraging laser trapping techniques, biocompatible nanoparticles, and advanced optical tweezers opens promising avenues for personalized and effective cancer therapy approaches.

Radiation doi: 10.3390/radiation4010006

Authors: Katsuhito Kino

To date, the radiation-adaptive response has been reported as a low-dose-related phenomenon and has been associated with radiation hormesis. Well-known cancers are caused by non-radiation active reactants, in addition to radiation. A model of suppression for radiation-specific cancers was previously reported, but the model did not target radiation-nonspecific cancers. In this paper, we describe kinetic models of radiation-induced suppressors for general radiation non-specific cancers, estimating the dose M that induces the maximum hormesis effect while satisfying the condition that the risk is approximately proportional to a dose above NOAEL (No Observed Adverse Effect Level). The radiation hormesis effect is maximal when the rate constant for generation of a risk-reducing factor is the same as the rate constant for its decomposition. When the two rate constants are different, the dose M at which the radiation hormesis effect is maximized depends on both rate constants, but the dose M increases as the two rate constants approach each other, reaching a maximum dose. The theory proposed in this paper can only explain existing experiments with extremely short error bar lengths. This theory may lead to the discovery of unknown risk-reducing factor at low doses and the development of risk-reducing methods in the future.

Radiation doi: 10.3390/radiation4010005

Authors: Aryan Safakish Lakshmanan Sannachi Amir Moslemi Ana Pejović-Milić Gregory J. Czarnota

(1) Background: Some cancer patients do not experience tumour shrinkage but are still at risk of experiencing unwanted treatment side effects. Radiomics refers to mining biomedical images to quantify textural characterization. When radiomics features are labelled with treatment response, retrospectively, they can train predictive machine learning (ML) models. (2) Methods: Radiomics features were determined from lymph node (LN) segmentations from treatment-planning CT scans of head and neck (H&N) cancer patients. Binary treatment outcomes (complete response versus partial or no response) and radiomics features for n = 71 patients were used to train support vector machine (SVM) and k-nearest neighbour (k-NN) classifier models with 1–7 features. A deep texture analysis (DTA) methodology was proposed and evaluated for second- and third-layer radiomics features, and models were evaluated based on common metrics (sensitivity (%Sn), specificity (%Sp), accuracy (%Acc), precision (%Prec), and balanced accuracy (%Bal Acc)). (3) Results: Models created with both classifiers were found to be able to predict treatment response, and the results suggest that the inclusion of deeper layer features enhanced model performance. The best model was a seven-feature multivariable k-NN model trained using features from three layers deep of texture features with %Sn = 74%, %Sp = 68%, %Acc = 72%, %Prec = 81%, %Bal Acc = 71% and with an area under the curve (AUC) the receiver operating characteristic (ROC) of 0.700. (4) Conclusions: H&N Cancer patient treatment-planning CT scans and LN segmentations contain phenotypic information regarding treatment response, and the proposed DTA methodology can improve model performance by enhancing feature sets and is worth consideration in future radiomics studies.

Radiation doi: 10.3390/radiation4010004

Authors: Gennady I. Zebrev Nikolay N. Samotaev Rustem G. Useinov Artur M. Galimov Vladimir V. Emeliyanov Artyom A. Sharapov Dmitri A. Kazyakin Alexander S. Rodin

A new physics-based compact model, which makes it possible to simulate in a unified way the neutrons and protons of cosmic ray-induced SEU cross-sections, including the effects from nuclear reaction products and from direct ionization by low-energy protons, has been proposed and validated. The proposed approach is analytical and based on explicit analytical relationships and approximations with physics-based fitting parameters. GEANT4 or SRIM numerical calculations can be used as an aid to adjust or refine the phenomenological parameters or functions included in the model, taking into account real geometrical configurations and chemical compositions of the devices. In particular, explicit energy dependencies of the soft error cross-sections for protons and neutrons over a wide range of nucleon energies were obtained and validated. The main application areas of the developed model include space physics, accelerator studies high energy physics and nuclear experiments.

Radiation doi: 10.3390/radiation4010003

Authors: Abida Sultana Jintana Meesungnoen Jean-Paul Jay-Gerin

Utilizing Monte Carlo multi-track chemistry simulations along with a cylindrical instantaneous pulse (Dirac) irradiation model, we assessed the initial acidic response in both subcritical and supercritical water under high radiation dose rates. This investigation spans a temperature range of 300 to 500 °C at a nominal pressure of 25 MPa, aligning with the operational conditions anticipated in proposed supercritical water (SCW)-cooled small modular reactors (SCW-SMRs). A pivotal finding from our study is the observation of a significant ‘acid spike’ effect, which shows a notable intensification in response to increasing radiation dose rates. Our results bring to light the potential risks posed by this acidity, which could potentially foster a corrosive environment and thereby increase the risk of accelerated material degradation in reactor components.

Radiation doi: 10.3390/radiation4010002

Authors: Yuri Sagisaka Yasuyuki Takahashi Shota Hosokawa Niina Kanazawa Hiroki Yamamoto Go Takai Keiji Nagano

We investigated imaging conditions for the distribution of lutetium oxodotreotide (Lu-177 DOTATATE) in the body during peptide receptor radionuclide therapy for neuroendocrine tumor (NET). We investigated imaging conditions using gamma rays emitted from the radionuclide. The gamma rays had energy peaks at 113 and 208 keV and characteristic X-rays at 56 keV. Image quality was compared by utilizing a combination of low–medium-energy general-purpose (LMEGP) and medium-energy general-purpose (MEGP) collimators. This study included the measurement of total spatial resolution (Full Width at Half Maximum) using a line source phantom. We compared the image quality of static images using a plane phantom and SPECT images using a cylindrical phantom. This comparison involved assessing recovery coefficient curves, count ratio, and %CV. Imaging evaluation was also performed on one NET patient. In phantom studies and the clinical study, comparing the combination of the three energy peaks (56 + 113 + 208 keV) using the LMEGP collimator and the conventional combination (113 + 208 keV) using the MEGP collimator revealed a count ratio of 1.9 times the maximum, stable %CV, and the best image quality.

Radiation doi: 10.3390/radiation4010001

Authors: Alfonso Balmori-de la Puente Alfonso Balmori

Cetaceans are cast to shore for a large number of reasons, although sometimes it is not clear why. This paper reviews the types and causes of cetacean strandings, focusing on mass strandings that lack a direct scientific explanation. Failure of cetacean orientation due to radiofrequency radiation and alterations in the Earth’s magnetic field produced during solar storms stand out among the proposed causes. This paper proposes the possibility that anthropogenic radiofrequency radiation from military and meteorological radars may also cause these strandings in areas where powerful radars exist. A search of accessible databases of military and meteorological radars in the world was carried out. Research articles on mass live strandings of cetaceans were reviewed to find temporal or spatial patterns in the stranding concentrations along the coast. The data showed certain patterns of spatial and temporal evidence in the stranding concentrations along the coast after radar setup and provided a detailed description of how radars may interfere with cetacean echolocation from a physiological standpoint. Plausible mechanisms, such as interference with echolocation systems or pulse communication systems, are proposed. This work is theoretical, but it leads to a hypothesis that could be empirically tested. Further in-depth studies should be carried out to confirm or reject the proposed hypothesis.

Radiation doi: 10.3390/radiation3040017

Authors: Nile E. J. Dixon Stephen D. Monk James Graham David Cheneler

Nuclear sites require regular measurements of the air, soil, and groundwater to ensure the safety of the surrounding environment from potentially hazardous levels of contamination. Although high-energy beta and gamma emitters can often be detected instantly using fixed dosimeters, the detection of low-energy beta emitters is a difficult challenge, especially in groundwater, as its radiation is easily self-absorbed by the surrounding medium. Therefore, it is common practice to sample groundwater and transfer it to a laboratory for analysis using Liquid Scintillation Counting. This work demonstrates a new detector design for the real-time monitoring of tritiated water, a weak beta emitter. This design utilizes a flow cell filled with a granulated scintillator to maximize the surface area of the sample. The cavity is made from plastic sheets, which allow rapid manufacture using readily available lamination sheets. A column of SiPMs in coincidence counting mode has been implemented to reduce noise and allow future extensions to the flow cell for greater detection rates while allowing the detector to fit within limited spaces such as groundwater monitoring boreholes. Using multiple concentrations of tritiated water, this detector has been validated and calibrated, obtaining a minimum detection activity of 26.356 ± 0.889 Bq/mL for a 1-day counting period.