Background and purpose:Clinical trials on ultrahypofractionated (UHF) whole‑breast radiotherapy demonstrated non‑inferiority to moderate hypofractionation (HF). However, real-world evidence using modern treatment techniques, captured by fully automated electronic patient-reported outcome measures (ePROM), remains limited. This study prospectively evaluated the clinical implementation of UHF whole-breast radiotherapy using intensity-modulated/volumetric arc radiotherapy (IMRT/VMAT) with ePROM-based adverse event monitoring. Materials and methods:In this single-centre prospective cohort, consecutive non-metastatic breast cancer patients (breast conserving surgery, no nodal and no boost irradiation) received either HF (15 × 2.67  Gy) or UHF (5 × 5.2  Gy). Acute and late side effects were assessed using PRO‑CTCAE items (itching, radiation skin reaction, skin darkening, pain and breast tenderness) via an automated ePROM platform at the first and last fraction, and at 3, 6, 9, 12, and 24  months. Longitudinal adverse event grades were modelled using population-averaged ordinal generalised estimating equations adjusted for age, surgery, and hormone therapy. Results:The patient cohort of 308 patients included 177 UHF and 131 HF patients. ePROM completion adherence was high (30% drop-out at 24 months). No clinically meaningful differences in adverse event severity were observed between both regimens, except for higher radiation skin reactions at the last fraction in HF (odd ratio (OR) = 2.70). At 24 months, only pain severity differed, with higher odds for HF (OR = 3.08). Other endpoints showed no significant between-group differences. Conclusion:UHF whole-breast radiotherapy delivered with contemporary IMRT/VMAT showed no increase in acute or late patient-reported adverse events compared with HF, confirming its safe integration into clinical routine.

Background: Outcomes of whole-pelvic radiotherapy (WPRT) in the era of moderately hypofractionated radiotherapy for prostate cancer remain sparsely reported. Previous studies indicate a high discrepancy between patient-reported outcomes (PROs) and clinician-reported outcomes (CROs) assessing the same endpoint. This study analyzed the concordance between PROs and CROs for WPRT and prostate-only radiotherapy (PRT) patients. Methods: Patients received a prescribed dose of 20 × 3 Gy to the planning target volume (PTV) and, in cases of lymph node involvement, 46 Gy to the regional lymph nodes. 176 WPRT and 62 PRT patients reported genitourinary (GU) and gastrointestinal (GI) adverse events through an electronic patient-reported outcome measures tool. Simultaneously, clinicians graded side effects using Radiation Therapy Oncology Group (RTOG) criteria for up to two years post-radiotherapy. Composite GU and GI PRO scores, derived by averaging endpoints, were evaluated for their ability to discriminate RTOG G1+ events via receiver operating characteristic curve analysis. Results: During treatment, WPRT patients exhibited elevated GI scores compared to PRT patients via PROs (mean: 2.80 vs. 2.48, p=0.010) and CROs (mean: 1.15 vs. 0.89, p=0.014), though levels equalized by 12 months. Composite PRO scores demonstrated moderate-to-good discriminatory performance for elevated CRO levels (areas under the curves: GI 0.65-0.74; GU 0.73-0.82) from the acute phase through 24 months. Conclusion: WPRT was associated with increased acute GI adverse effects but showed recovery to PRT levels within one year. Results demonstrated that PROs yield clinically relevant discriminatory value. Routine integration of PROs may facilitates earlier adverse event identification, allocation of clinical resources, and individualized clinical decision-making.

Oligometastatic cancer is characterised by a low volume of metastases to a small number of anatomical sites. However, evaluating the impact of metastases-directed therapies (MDTs) on overall survival or quality of life is often challenging. Current clinical trials use a wide range of primary endpoints that might not be validated or suited to MDT. To address this issue, we did a systematic review of international trial registries, alongside a Delphi consensus process involving 30 experts and five patient representatives. The aim was to identify preferred primary endpoints for MDT trials in oligometastatic disease, regardless of tumour type. Overall survival and progression-free survival were the most frequently used endpoints across the 121 comparative trials reviewed. Over four Delphi consensus rounds, overall survival had the highest level of agreement, although its limitations as a sole endpoint were emphasised. In addition to the widely used progression-free survival endpoint, polymetastatic progression-free survival and start-or-switch of systemic therapy-free survival also reached consensus, particularly for trials integrating systemic therapies. Both polymetastatic progression-free survival and systemic therapy-free survival permit repeat MDT without classifying it as treatment failure. Patient representatives highlighted the importance of time-to-deterioration of quality of life. This consensus supports overall survival as a primary endpoint and, in addition to progression-free survival, recommends polymetastatic progression-free survival and systemic therapy-free survival, especially in combination with systemic therapies. Adopting these endpoints will make MDT trials more relevant, comparable, and patient-centred, thereby empowering future clinical and policy decisions.

Pancreatic ductal adenocarcinoma (PDAC) is the most frequent type of pancreatic cancer with a poor prognosis and resistance to conventional radio- and chemotherapy. Radiation can induce pro-inflammatory signaling by activating the type 1 interferon (IFN-I) response, which can be enhanced by targeting negative regulators of the IFN-I pathway, such as ADP-ribosyltransferase PARP7. Here, we show that PARP7 inhibitors (PARP7i) enhance radiation-induced cell death and promote STING- and NF-κB-dependent immunogenic signaling in PDAC cells, leading to inflammatory gene expression and cytokine release. These effects were most pronounced in BxPC-3 cells, which exhibit higher baseline expression of PARP7, AHR, and interferon response genes. PARP7i potentiated the immunogenic effects of hypofractionated radiation by inducing a STING-dependent IFN-I response, leading to immunogenic cell death and activation of monocytes and NK cells. Carbon ion irradiation elicited stronger immunogenicity than X-rays when combined with PARP7i. KRAS-mutated PANC-1 cells showed a higher expression of enzymes that convert ATP to immunosuppressive adenosine, which was enhanced by radiation. This may explain why PARP7i were more effective as monotherapy in PANC-1 cells, promoting NK cell activation. These findings support further evaluation of PARP7i in PDAC in combination with radiotherapy or as monotherapy, depending on the immunosuppressive effects of radiation.

PURPOSE:Pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge characterized by an alarmingly low survival rate. Despite surgical advances and new chemotherapy combinations, currently available treatment fails to improve the overall survival of PDAC patients largely due to an immunosuppressive tumor microenvironment. Radiation can induce cell death and reprogramme the tumor microenvironment by promoting anti-tumor immune response. The cGAS-STING and RIG-I-MAVS pathways are central components of the innate immune system that detect cytosolic nucleic acids and initiate type I interferon production. This study aims to leverage radiation-induced DNA damage together with inhibition of DNA repair and cell cycle checkpoints to potentiate type I interferon response and thereby enhance anti-tumor immunogenicity in PDAC. MATERIALS AND METHODS:Two different PDAC cell lines (KRAS wild-type BxPC-3 and KRAS-mutated PANC-1) were used to test two different radiation modalities (X-rays and carbon ions) and regimens (single and hypofractionated dose) in combination with ATR and CHK1 inhibitors as well as the STING agonist diABZI. Cell survival, immunogenic cell death, accumulation of cytosolic dsDNA and micronuclei, gene expression profiles, and STING- and NF-κB-dependent immune signaling were assessed. Immune activation was evaluated by incubating immune cells with supernatants from PDAC cells, followed by analysis of activation markers using spectral flow cytometry. RESULTS:Here we demonstrate that ATR inhibition sensitizes BxPC-3 cells to the cytotoxic effects of radiation and potentiates the immunogenic effects of carbon ions and hypofractionated X-rays (3x8 Gy). Increased accumulation of cytosolic dsDNA and micronuclei was coupled with STING-dependent IFNB1 secretion and genome-wide induction of inflammatory gene expression programs, ultimately resulting in the activation of monocytes. This was not the case for PANC-1 cells, where radiation alone exerted immunosuppressive effects on monocytes. CONCLUSIONS:Our results support further evaluation of ATR inhibition in combination with radiotherapy in KRAS wild-type pancreatic cancer.

PURPOSE:Although radiotherapy is a cornerstone of multidisciplinary cancer care, radiation oncology research represents only a small proportion of the oncology research portfolio. Several factors intrinsic to radiotherapy, such as the incremental nature of technological advances, the reliance on long-term clinical endpoints, or the substantial upfront investments required to investigate innovative radiotherapy technologies, pose challenges to conducting randomized controlled trials. Alternative, blended approaches to evidence generation are therefore required to assess the breadth of radiotherapy innovations. METHODS:The European Society for Radiotherapy and Oncology and the European Organisation for Research and Treatment of Cancer launched E2-RADIatE (EORTC-ESTRO RADiotherapy Infrastructure for Europe; EORTC 1811 - NCT03818503) in 2019. This pragmatic, observational, prospective multi-cohort study uses a centralised database to collect real-world data on cancer patients, their radiotherapy treatments, and outcomes across Europe. It aims to generate evidence and new hypotheses to assess radiotherapy innovations. RESULTS:After five years, two cohorts (OligoCare and ReCare) are actively recruiting patients. The platform has enabled the generation of new research hypotheses and the testing of innovative methodological strategies with the opening of the first international oncology Trial Within Cohorts (TWiCs). Engagement of the international radiotherapy community has been central to the development and sustainability of the infrastructure, while several barriers and limitations inherent to this type of real-world research have also been identified. CONCLUSION:The five-year experience of E2-RADIatE demonstrates the feasibility and added value of a large-scale, prospective, real-world, multi-cohort infrastructure to support evidence generation in radiotherapy, while highlighting regulatory and methodological challenges that must be addressed to maximise impact.

Background/Objectives: In recent years, neoadjuvant chemoimmunotherapy followed by surgery has improved outcomes in patients with stage II/III non-small cell lung cancer (NSCLC). However, the prognostic impact of residual mediastinal nodal disease after chemoimmunotherapy remains insufficiently defined, particularly with the introduction of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) 9th edition nodal subclassification. Methods: In this retrospective study, 90 consecutive patients with clinically node-positive (cN1-2) resectable locally advanced NSCLC who underwent neoadjuvant chemoimmunotherapy followed by curative-intent resection were included. Disease-free survival (DFS) was analyzed according to postoperative pathologic nodal status. Nodal status was assessed using the UICC/AJCC 8th edition (ypN0, ypN1, ypN2) and reclassified according to the 9th edition (ypN0, ypN1, ypN2a, ypN2b). Residual postoperative nodal disease was defined as residual pathologic nodal involvement (ypN+) in patients with clinically node-positive (cN+) disease at baseline. Results: The cohort comprised 90 patients (60% male, median age 63 years [interquartile range (IQR) 58–69]). Following neoadjuvant therapy, surgery revealed pathologic nodal clearance in 53 (58.9%) and residual nodal disease in 37 (41.1%) patients (ypN1, n = 16 [17.8%]; ypN2a, n = 15 [16.7%]; and ypN2b, n = 6 [6.7%]). DFS differed significantly by postoperative nodal status (global log-rank p < 0.001), with progressively poorer outcomes with increasing residual nodal burden. Conclusions: Residual nodal disease after neoadjuvant chemoimmunotherapy and surgery is associated with progressively inferior DFS according to its anatomic extent. The UICC/AJCC 9th-edition staging system provides clinically relevant prognostic granularity, supporting further investigation of mediastinal restaging and postoperative treatment strategies.

Abstract Background Secondary malignancies following multimodal oncological treatment are rare but represent a severe long-term complication, particularly in pediatric patients. Systematic analyses in pediatric neuro-oncology are currently lacking. Methods Based on the complete institutional pediatric neuro-oncology database, patients who developed a secondary malignancy during follow-up were identified. Extracranial secondary malignancies and meningiomas were detected using assigned ICD codes (C diagnoses excluding C71 or D32), extracted via an algorithm-based approach. Intracerebral secondary malignancies were identified through an algorithm-driven analysis of all tumor board decisions, using both keyword-based text search and a large language model. Clinical data were retrieved from the hospital patient information system. Results Among a total of 1823 patients in the pediatric neuro-oncology database, 28 patients with 34 secondary malignancies were identified. The most frequent primary tumors were medulloblastoma (n = 13), ependymoma (n = 3), and atypical teratoid/rhabdoid tumor (ATRT; n = 3). Most patients (n = 21) had been treated with craniospinal irradiation, there were only 5 patients with no documented radiotherapy. Likewise, only 7 patients had not undergone chemotherapy for the primary tumor. The most common secondary malignancies were high-grade gliomas (n = 9), meningiomas (n = 7), leukemias (n = 6), and thyroid carcinomas (n = 4). Latency periods varied substantially, ranging from 6.2 years for leukemias to 17.2 years for meningiomas. While thyroid carcinomas and meningiomas showed excellent prognosis, survival in patients with secondary high-grade gliomas was severely limited. Conclusions The applied information technology–based methods successfully identified patients with secondary malignancies within a comprehensive pediatric neuro-oncology database. The observed tumor entities correspond to expected patterns, with primary tumors amenable to curative multimodal therapy and typical secondary malignancies. Further analyses focusing on clinical risk factors and molecular characteristics of neuro-oncological secondary malignancies are planned.

Glioblastoma (GBM) is the most lethal form of brain cancer with an immunosuppressive tumor microenvironment (TME). Radio- and chemotherapy can modify the TME and elicit anti-tumor immunity through the STING and type I interferon (IFN-I) pathways. STING agonists or DNA damage response inhibitors can potentiate the effects of radiation by targeting the IFN-I pathway. Here, we examined the immunogenic response of GBM cells to hypofractionated or single-dose radiation combined with a STING agonist or inhibitors targeting immune signaling (PARP7), the DNA damage response, cell cycle checkpoints or autophagy. We found that hypofractionated radiation elicited a ferroptosis-dependent IFN-I response and that the PARP7 inhibitor KMR-206 and the STING agonist diABZI enhanced the effects of radiation by activating immune cells. In patient-derived GBM cancer stem cells with low STING levels, the PARP7 inhibitor was more effective at inducing immunogenic signaling compared to the STING agonist. Our results highlight the potential of PARP7 inhibitors as a new treatment to boost anti-tumor immunity in GBM, which may be more advantageous compared to STING agonists given that STING is often downregulated in GBM.

Background/Objectives: Malignant pleural mesothelioma (MPM) remains challenging to treat, with a poor prognosis. As controversy about clinical management continues, predictive biomarkers for patient selection to indicate the benefit of treatment modalities are urgently needed. Methods: In a retrospective analysis of 195 patients between 1994 and 2020 at the Department of Thoracic Surgery, Medical University of Vienna, Austria, the Mesothelioma Systemic Inflammation Score (MSIS)—consisting of pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), and fibrinogen—was tested for its prognostic and predictive significance. The prognostic impact of MSIS was subsequently validated in an independent cohort of 80 patients treated at the Department of Thoracic Surgery, Karl Landsteiner Institute for Clinical and Translational Thoracic Surgery Research, Clinic Floridsdorf, Vienna, Austria. Results: Median overall survival (OS) was 14 months for the entire cohort (95% CI: 11.4–16.6). Patients undergoing multimodality treatment including macroscopic complete resection had a longer OS (22.3 months, 95% CI: 18.6–26.0; p < 0.001). In multivariable analysis, MSIS (p < 0.001), disease stage (p = 0.001), and the type of treatment (p = 0.004) were confirmed as independent predictors for OS. Higher MSIS was associated with shorter OS (p < 0.001). Significant survival benefit of multimodality regimens including surgery was limited to patients with low MSIS. Among patients with low (≤ 2) MSIS, multimodality therapy was associated with significantly prolonged OS when compared with chemo- and/or radiotherapy alone (25.8 months [95% CI: 16.4–35.3] vs. 14.4 months [95% CI: 10.4–18.4], p < 0.001). In contrast, among patients with elevated MSIS, no survival benefit was achieved by surgery over conservative treatment (11.8 months [95% CI: 8.3–15.3] vs. 8.2 months [95% CI: 5.2–11.3], p = 0.233). The ability of MSIS to predict survival was equivalent between the baseline and the independent validation cohort (p < 0.001). Conclusions: The Mesothelioma Systemic Inflammation Score was found to be an independent prognostic score in pleural mesothelioma, predicting benefit from macroscopic complete resection as part of multimodality treatment in distinct patients.

Background/Objectives: This proof-of-concept study evaluated whether optical coherence tomography angiography (OCTA) can non-invasively capture micro-vascular alterations in non-melanoma skin cancer (NMSC) lesions during and after superficial orthovoltage radiotherapy (RT) using radiomics and vascular features analysis. Methods: Eight patients (13 NMSC lesions) received 36–50 Gy in 6–20 fractions. High-resolution swept-source OCTA volumes (1.1 × 10 × 10 mm3) were acquired from each lesion at three time points: pre-RT, immediately post-RT, and three months post-RT. Additionally, healthy skin baseline was scanned. After artifact suppression and region-of-interest cropping, (i) first-order and texture radiomics and (ii) skeleton-based vascular features were extracted. Selected features after LASSO (least absolute shrinkage and selection operator) were explored with principal-component analysis. An XGBoost model was trained to classify time points with 100 bootstrap out-of-bag validations. Kruskal–Wallis tests with Benjamini–Hochberg correction assessed longitudinal changes in the 20 most influential features. Results: Sixty-one OCTA volumes were analyzable. LASSO retained 47 of 103 features. The first two principal components explained 63% of the variance, revealing a visible drift of lesions from pre- to three-month post-RT clusters. XGBoost achieved a macro-averaged AUC of 0.68 ± 0.07. Six features (3 texture, 2 first order, 1 vascular) changed significantly across time points (adjusted p < 0.05), indicating dose-dependent reductions in signal heterogeneity and micro-vascular complexity as early as treatment completion, which deepened by three months. Conclusions: OCTA-derived radiomic and vascular signatures tracked RT-induced micro-vascular remodeling in NMSC. The approach is entirely non-invasive, label-free, and feasible at the point of care. As an exploratory proof-of-concept, this study helps to refine scanning and analysis protocols and generates knowledge to support future integration of OCTA into adaptive skin-cancer radiotherapy workflows.

PURPOSE:To demonstrate a data-driven risk management (RM) strategy in radiation oncology using an in-house developed web-based incident reporting system. The system leverages real-time analytics to enhance clinical risk prioritization and management, improving patient safety and treatment efficiency. METHODS:We developed and implemented a web-based incident reporting system that allows any staff member to report incidents in real time, supporting anonymous submissions and capturing detailed incident data. The collected data are followed up in monthly meetings of a dedicated multidisciplinary RM team that decides on respective interventions. Over five years, incident data were analyzed to assess the effectiveness of safety barriers-pre-planning, physics, and pre-treatment checks-in capturing incidents before they impact patient care and safety. The analysis focused on incident frequencies and the workflow steps where errors originated versus where they were detected, highlighting deficiencies and guiding improvements. When specific issues increased, a Failure Mode and Effects Analysis (FMEA) was initiated to identify and prioritize failure modes and implement corrective actions, such as new safety barriers or refining existing safety measures. RESULTS:The web-based incident reporting system enhances responsive incident reporting and tailors RM strategies effectively. Data analysis reveals incident frequencies and detection points, identifying errors that bypass safety barriers and enabling targeted countermeasures. Despite safety barriers intercepting many incidents, critical gaps were identified. Since implementing data-driven RM in 2019, the average number of process steps between incident cause and detection could be halved. Resource analysis indicates increased allocation is needed; development required approximately 150 h, and RM averages 20% of a full-time equivalent position. CONCLUSION:Implementing the web-based incident reporting system has advanced RM in radiation oncology, ensuring legal compliance and enhancing safety through real-time analytics. The system effectively identifies and mitigates risks, strengthening QA barriers as evidenced by decreased time between error origin and detection. Adequate resource allocation is essential to sustain these improvements. Increasing full-time equivalent allocations for RM activities is recommended.

Objective. For surface-based breathing motion prediction, which is essential to overcome inherent system latencies of active motion management strategies in radiotherapy, long short-term memory (LSTM) networks and related networks—bidirectional LSTMs (BiLSTMs), gated recurrent units (GRUs), and BiGRUs—have shown promise, primarily for prediction horizons around 500 ms. The novel temporal Kolmogorov–Arnold networks (TKANs), and BiTKANs remain unexplored for this application. Therefore, this study aimed at assessing the performance of the above six networks for different prediction horizons up to 1000 ms. Approach. C-Rad Sentinel (C-Rad AB, Sweden) breathing signals were retrospectively collected for 207 patients. Signals from 41 patients were used for model testing, while the remaining data sets were 9:1 split for training and validation. Pre-processing included cropping, low-pass filtering, re-sampling, and scaling. Signals were cut into 8 s segments as input for the prediction models with a corresponding true label. A grid search was performed to optimize hyperparameters for each of the six network types using a prediction horizon of 500 ms. Subsequently, each network was trained ten times with these parameters across various training:validation splits, evaluating ten prediction horizons between 100 ms and 1000 ms. Root mean square errors (RMSEs) between the predicted breathing amplitudes and the true labels as well as inference times were calculated on the test set. Main results. The hyperparameter-tuning resulted in a lowest mean RMSE of 57 ± 39 μ m for the LSTM, while a mean RMSE of 88 ± 35 μ m was obtained for the TKAN. TKANs were fastest to infer, averaging 10.2 ms per prediction. Increasing prediction horizons resulted in moderate increases of RMSEs up to 113 μ m for horizons below 600 ms. RMSEs remained below 500 μ m for horizons up to 1000 ms. Significance . The LSTM outperforms newer networks for most prediction horizons. All models showed feasibility for a wide range of prediction horizons and the effect of the prediction horizon on the RMSE was assessed.

The increasing prevalence of inflammatory bowel disease (IBD) and rising pollution from micro- and nanoplastic (MNP) particles has prompted investigations on their potential interconnection. To elucidate the complex relationship between IBD and exposure to MNPs, we induced colitis in mice using dextran sodium sulfate (DSS) and orally administered a mixture of polystyrene (PS) MNPs (diameter 10, 1, and 0.29 µm). These particles enabled a detailed examination of MNP biodistribution, innate immune cell response and gut microbiome alterations under inflammatory conditions. Specifically, the nanosized PS particles predominantly accumulated in the bloodstream and excretory organs, with enhanced accumulation in the inflamed gut/colon. Proteomic analysis of the colon revealed alterations in molecular pathways related to protein transport, metabolism, and immune responses. Specifically, we found macrophage proteome signatures with pro-inflammatory polarization, highlighting the intricate effects of MNPs on inflammation and immune cell behavior. Moreover, MNPs significantly disrupted the gut microbiome, reducing microbial diversity and shifting bacterial populations towards pro-inflammatory and potentially pathogenic species. These changes suggest that MNP exposure could exacerbate colitis through complex interactions involving MNPs, immune responses, and microbial dynamics. The widespread presence of MNPs underscores the urgent need for comprehensive strategies to address MNP pollution, its implications for disease, and potential impacts on public health.

Background and Objective: Due to the increasing use of imaging and lung cancer screening programs, the rate of detected pulmonary nodules has steadily increased over the past decade. Overall, the diagnosis and management of pulmonary nodules remain challenging. Moreover, no specific guidelines exist for the management of pulmonary nodules in patients with a history of previous malignancy. This study reflects the current management in a real-world setting in a specialized European center. Methods: In this retrospective single-center study, patients with a pulmonary nodule <3 cm referred to the Division of Pulmonology or the Department of Thoracic Surgery at the Medical University of Vienna, Austria, from November 2022 to July 2024, were analyzed. A subgroup analysis of patients with a history of previous malignancy was performed and compared to patients without previous malignancies. Results: In total, 356 patients (48.5% male, median age 67 years [IQR 61–74], 53.7% with a history of previous cancer) with a pulmonary nodule (mean size of 14.8 mm) were enrolled. Bronchoscopy, computed tomography (CT)-guided biopsy, or surgery was performed in 13.2%, 7.3%, and 65.2% of the cases, respectively. The overall malignancy rate was 70.5%. Pulmonary nodules in patients with a prior malignancy were significantly larger (p < 0.001), showed a progression in size (p < 0.001), and were found to be malignant more frequently when compared to patients without previous cancer (p = 0.032). Conclusions: As most patients referred to a specialized center represent a selected group of high-risk patients, the majority of pulmonary nodules were found to be malignant. In patients with a history of previous malignancy, tissue sampling is warranted as the rate of malignancy is high.

BACKGROUND:In magnetic resonance (MR)-only radiotherapy (RT) workflows, synthetic computed tomography images (sCT) are needed as a surrogate for a dose calculation. Commercial and certified sCT algorithms became recently available, but many have not been evaluated in a clinical setting, especially in the head and neck tumor (HN) region. In this study, an MRI-only workflow using a commercial sCT generator for photon beam therapy in brain and HN body sites was evaluated in terms of dose calculation accuracy, modelling of immobilization devices, as well as usability for autosegmentation. METHODS:For 13 brain and 10 HN cancer patients, MR scans using T1W mDIXON sequences were retrospectively collected. Four brain and all HN patients were scanned in RT treatment position with immobilization devices. All MRIs were converted to a sCT using the MRCAT algorithm (Philips, Eindhoven, The Netherlands). All patients underwent standard planning CT (pCT) for clinical segmentation and VMAT treatment planning. The sCT was rigidly registered to the pCT and clinical contours were transferred to the sCT. For dosimetric evaluation of sCT based dose calculation, all VMAT plans were recalculated on the sCT. D1% and Dmean were compared for all structures between pCT and sCT, but D95%, D98% for targets only. For MR-invisible RT immobilization device modelling, MR-visible markers were placed into sCT and a geometric robustness analysis was performed based on the same target dose-volume parameters. For organs-at-risk (OARs) autosegmentation, both pCT and sCT were autosegmented with a clinically established CT-based autocontouring software. The agreement of contours on pCT and sCT was analyzed by similar dose-volume parameters and dice similarity (DSC) and Hausforff distance (HD). RESULTS:The overall median deviation (± interquartile range) of dosimetric parameters between sCT and pCT including the immobilization model was 1.1 ± 0.4% for brain target volumes, 1.3 ± 1.2% for brain OAR, 0.4 ± 0.7% for HN target volumes and 0.4 ± 0.9% for HN OAR. The median geometric agreement over all sCT autocontours compared to pCT autocontours resulted in DSC = 0.82 for brain OAR and DSC = 0.79 for HN OAR. CONCLUSION:MR-only RT planning using MRCAT software package was feasible for brain and HN tumors, with acceptable clinical accuracy. The MR-invisible immobilization devices could be modelled in the planning system and the autosegmentation on sCTs using a CT-based autosegmentation tool was feasible.