Abstract Background Magnetic resonance imaging (MRI) offers superior soft-tissue contrast and MRI-only radiotherapy (RT) eliminates uncertainties associated with computed tomography (CT)-to-MRI image registration. An MRI-only RT workflow in patients with hip prostheses remains challenging since delineation, synthetic CT (sCT) generation, and marker identification ideally rely on MR images, which are sensitive to distortions. Metal-artifact reduction sequences (MARS) mitigate metal distortions but often obscure gold markers. The aim of this study is to present a proof-of-concept 3 T MRI-only RT workflow for prostate cancer patients with hip prostheses, using only MARS MAVRIC-SL (GE HealthCare) for delineation, sCT generation and fiducial marker identification. Methods Five prostate cancer patients with one or two hip prostheses and intraprostatic fiducial markers underwent CT, standard 3 T MRI and additional MAVRIC-SL MRI. All images were used retrospectively and did not affect patient treatment. Delineation and sCT generation were performed using MAVRIC-SL. Intraprostatic markers were not visible in MAVRIC-SL due to artifact suppression; instead, raw data were reconstructed into spectral-bin images to manually identify the markers. To prevent incoming radiation from passing through the implants and reduce the associated uncertainties in dose calculation and treatment delivery, beam avoidance sectors (AS) were applied. Conventional CT-based avoidance sectors were registered to the sCT and defined as AS1. Prosthesis-induced signal voids in MAVRIC-SL were used to define AS2. Two treatment plans (42.7 Gy, 7 fractions) were created per patient using AS1 and AS2. Plans were compared using dose-volume histogram (DVH) parameters. AS2-plans were recalculated on registered CTs for DVH-comparison and gamma analyses (2%/2 mm and 1%/1 mm with 10% dose threshold) were performed. Results Delineation, marker identification and sCT generation were successful using MAVRIC-SL. Median dose differences between AS1 and AS2 remained within ± 0.1% for PTV, while OAR metrics ranged from − 0.4% to + 0.7%. AS2-plans recalculated on CT showed dose differences ≤ 0.9% for PTV and ≤ 1% for OARs. Median gamma pass rates were 99.1% (2%/2 mm) and 96.4% (1%/1 mm). Conclusions This study demonstrates the feasibility of an MRI-only radiotherapy workflow at 3 T for prostate cancer patients with hip prostheses, enabling delineation, sCT generation, dose calculation and marker identification from a single MAVRIC-SL acquisition. Clinical trial number Not applicable.
Abstract Background Concurrent cisplatin and radiotherapy frequently cause severe acute hematologic toxicity. This study investigated whether lymphocyte apoptosis, quantified via the γ-H2AX pan-nuclear immunostaining assay, can serve as a reliable biomarker for the acute hematologic side effects of combined chemoradiation. Methods Blood samples were collected from cancer patients and healthy controls. Lymphocyte apoptosis was evaluated using the γ-H2AX pan-nuclear assay following in vitro and in vivo exposure to cisplatin and ionizing radiation (IR). In PBMCs, γ-H2AX results strongly correlated with conventional caspase-3 (r = 0.9736) and annexin V (r = 0.9780) apoptosis assays. Additionally, in vitro experiments assessed how phytohemagglutinin-L (PHA-L)-induced lymphocyte proliferation influences the combined effects of cisplatin and IR on apoptosis, alongside the regulatory role of the ATM protein. Results In vitro, cisplatin increased lymphocyte apoptosis asymptotically, plateauing at 10 µg/ml (11.6 ± 5.0%). Combined cisplatin and IR treatment increased apoptosis in a strictly additive manner (radiation effect: p < 0.0001), with no significant synergistic interaction effect between the two modalities (p = 0.22). The apoptotic effect level of in vivo cisplatin administration did not differ significantly from the maximum effect observed following a 1-hour in vitro exposure to high cisplatin concentrations. In vivo, the additive effect of cisplatin on IR-induced apoptosis peaked up to 3 days post-administration before returning to baseline by day 6. Consistent with these findings, cisplatin and radiation induced a significant, additive increase in apoptosis within PHA-L-stimulated lymphocytes. Inhibition of ATM has no effect on apoptosis following treatment with cisplatin and IR. Conclusions The γ-H2AX pan-nuclear assay provides a valid, reliable method for quantifying radiation- and chemotherapy-induced lymphocyte damage. The time-dependent, additive toxicity observed indicates a critical clinical window (up to 3 days post-cisplatin) for maximum hematologic damage, allowing for optimization of treatment schedules. Clinical trial number Not applicable.
Abstract Purpose Deep inspiration breath hold (DIBH) is widely used to reduce cardiac dose in left-sided breast radiotherapy. However, the reliability of DIBH at CT simulation, has not been systematically evaluated despite the importance of CT simulation as the basis for treatment planning. We investigated the clinical impact of surface-guided breathing training on DIBH reliability and cardiac dose sparing. Methods In this retrospective cohort study, 115 breast cancer patients undergoing DIBH CT simulation were analyzed before and after implementation of surface-guided breathing training using an SGRT system. DIBH performance was quantified by partial lung volume increase (PLVI) and breath-hold variability. Correlations between external surface motion and internal DIBH depth were assessed. Cardiac dose metrics were compared, with a subgroup analysis for patients receiving lymphatic drainage area (LDA) irradiation. Results Prior to training, insufficient DIBH CTs—including negative PLVI cases—were observed. After training implementation, all CT scans were acquired in intended breath-hold states, eliminating insufficient DIBH acquisitions. Mean PLVI increased by ~ 9%, and breath-hold variability decreased by ~ 26%. Sternum motion correlated most strongly with PLVI, with multiregion surface monitoring yielding the highest internal correlation. These improvements were reflected in significant reductions in cardiac dose, particularly in the LDA subgroup, with selected heart dose metrics reduced up to 96%, while maintaining target coverage. Conclusions DIBH at CT simulation with surface-guided breathing training proves to be reliable. The training prevents planning CTs in wrong breathing states and thus enables clinically meaningful cardiac dose reduction in breast radiotherapy.
Abstract Background Deep inspiration breath-hold (DIBH) is a radiotherapy standard technique for cardiac-sparing in breast cancer, particularly for left-sided tumors. However, not all patients can successfully complete DIBH RT in clinical routine, necessitating conversion to free breathing (FB) techniques and replanning. This study aimed to identify clinical factors predictive of DIBH feasibility to optimize patient selection and resource utilization. Methods This retrospective study analyzed all patients ( n = 1920) who underwent curative postoperative breast cancer radiotherapy at our institution between May 2020 and December 2024. All patients underwent initial DIBH feasibility assessment and were evaluated for completion of radiotherapy with DIBH or conversion to FB technique. A detailed subanalysis was performed for all patients treated in 2023 ( n = 470). Patient-related factors including age, body mass index (BMI), Karnofsky Performance Status (KPS), Charlson Comorbidity Index (CCI), pulmonary comorbidities, smoking status, and geometric surface distance between DIBH and FB planning scans were collected for the subanalysis. Results Across the entire cohort (years 2020–2024) of 1,920 patients, 78 replannings (4%) occurred due to conversion from DIBH to free breathing. Increasing age (cut-off of 63 years) was significantly associated with higher replanning rates ( p = 0.001). In the 2023 subanalysis ( n = 470), pulmonary comorbidities ( p = 0.008), higher CCI ( p = 0.044), and a geometric surface distance of below 1 cm between DIBH and FB CT scans ( p = 0.0001) were significant predictors of replanning. The Karnofsky Performance Score, BMI, and smoking status showed no significant association with replanning. Conclusions Age, pulmonary comorbidities, overall comorbidity burden, and insufficient geometric displacement are significant predictors of DIBH failure in breast cancer radiotherapy. These readily available clinical parameters can optimize patient selection algorithms and inform decisions regarding dual CT simulation workflows. A risk-stratified approach incorporating these factors may reduce unnecessary imaging, decrease planning burden, and improve resource allocation while maintaining optimal cardiac protection for appropriate candidates. Clinical trial number The study was registered in the German Clinical Trials Register (DRKS; registration number: DRKS00038550) on 22 December 2025 ( https://www.drks.de/ ).
The sparing effect of FLASH irradiation with ultrahigh dose rates (UHDR), by applying high dose fractions in less than one second, on adverse reaction in many normal tissues but not on tumour control has the potential to widen the therapeutic window and advance cancer radiotherapy. However, the mechanism is poorly understood, preventing its optimal application in the clinic. Here we review the current knowledge of radiation-induced radicals and their reactions, including time factors which are rarely considered. Furthermore, experimental in vitro and in vivo data in the framework of prevailing hypotheses, and the role of low oxygen concentrations and reoxygenation, are discussed. Finally, potential protective mechanisms are considered based on such reactions and the role of oxygen. We argue that more than one mechanism may contribute to dose-rate dependent protection, and that differences exist between protective mechanisms in vitro and in vivo. Furthermore, we propose a new protective reaction linking radiation chemistry to the role of oxygen in FLASH irradiation and incorporating the differential responses of normal tissue and tumours.
