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Background: This study aimed to develop an automated algorithm to noninvasively distinguish gliomas from other intracranial pathologies, preventing misdiagnosis and ensuring accurate analysis before further glioma assessment., Methods: A cohort of 1280 patients with a variety of intracranial pathologies was included. It comprised 218 gliomas (mean age 54.76 ± 13.74 years; 136 males, 82 females), 514 patients with brain metastases (mean age 59.28 ± 12.36 years; 228 males, 286 females), 366 patients with inflammatory lesions (mean age 41.94 ± 14.57 years; 142 males, 224 females), 99 intracerebral hemorrhages (mean age 62.68 ± 16.64 years; 56 males, 43 females), and 83 meningiomas (mean age 63.99 ± 13.31 years; 25 males, 58 females). Radiomic features were extracted from fluid-attenuated inversion recovery (FLAIR), contrast-enhanced, and noncontrast T1-weighted MR sequences. Subcohorts, with 80% for training and 20% for testing, were established for model validation. Machine learning models, primarily XGBoost, were trained to distinguish gliomas from other pathologies., Results: The study demonstrated promising results in distinguishing gliomas from various intracranial pathologies. The best-performing model consistently achieved high area-under-the-curve (AUC) values, indicating strong discriminatory power across multiple distinctions, including gliomas versus metastases (AUC = 0.96), gliomas versus inflammatory lesions (AUC = 1.0), gliomas versus intracerebral hemorrhages (AUC = 0.99), gliomas versus meningiomas (AUC = 0.98). Additionally, across all these entities, gliomas had an AUC of 0.94., Conclusions: The study presents an automated approach that effectively distinguishes gliomas from common intracranial pathologies. This can serve as a quality control upstream to further artificial-intelligence-based genetic analysis of cerebral gliomas., Competing Interests: The authors declare no potential conflicts of interest., (© The Author(s) 2025. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Despite their unique histologic features, gliosarcomas belong to the group of glioblastomas and are treated according to the same standards. Fibroblast activation protein (FAP) is a component of a tumor-specific subpopulation of fibroblasts that plays a critical role in tumor growth and invasion. Some case studies suggest an elevated expression of FAP in glioblastoma and a particularly strong expression in gliosarcoma attributed to traits of predominant mesenchymal differentiation. However, the prognostic impact of FAP and its diagnostic and therapeutic potential remain unclear. Here, we investigate the clinical relevance of FAP expression in gliosarcoma and glioblastoma and how it correlates with 68 Ga-FAP inhibitor (FAPI)-46 PET uptake. Methods: Patients diagnosed with gliosarcoma or glioblastoma without sarcomatous differentiation with an overall survival of less than 2.5 y were enrolled. Histologic examination included immunohistochemistry and semiquantitative scoring of FAP (0-3, with higher values indicating stronger expression). Additionally, 68 Ga-FAPI-46 PET scans were performed in a subset of glioblastomas without sarcomatous differentiation patients. The clinical SUVs were correlated with FAP expression levels in surgically derived tumor tissue and relevant prognostic factors. Results: Of the 61 patients who were enrolled, 13 of them had gliosarcoma. Immunohistochemistry revealed significantly more FAP in gliosarcomas than in glioblastomas without sarcomatous differentiation of tumor tissue ( P < 0.0001). In the latter, FAP expression was confined to the perivascular space, whereas neoplastic cells additionally expressed FAP in gliosarcoma. A significant correlation of immunohistochemical FAP with SUV mean and SUV peak of 68 Ga-FAPI-46 PET indicates that clinical tracer uptake represents FAP expression of the tumor. Although gliosarcomas express higher levels of FAP than do glioblastomas without sarcomatous differentiation, overall survival does not significantly differ between the groups. Conclusion: The analysis reveals a significant correlation between SUV mean and SUV peak in 68 Ga-FAPI-46 PET and immunohistochemical FAP expression. This study indicates that FAP expression is much more abundant in the gliosarcoma subgroup of glioblastomas. This could open not only a diagnostic but also a therapeutic gap, since FAP could be explored as a theranostic target to enhance survival in a distinct subgroup of high-risk brain tumor patients with poor survival prognosis., (© 2024 by the Society of Nuclear Medicine and Molecular Imaging.)

To evaluate the prognostic value of biomarkers from peripheral blood obtained as routine laboratory assessment for overall survival in a cohort of stage III non-small cell lung cancer (NSCLC) patients treated with definitive radiochemotherapy at a high-volume cancer center. Seven blood biomarkers from 160 patients treated with definitive radiochemotherapy for stage III NSCLC were analyzed throughout the course treatment. Parameters were preselected using univariable and multivariable proportional hazards analysis and were assessed for internal validity using leave-one-out cross validation. Cross validated classifiers including biomarkers in addition to important clinical parameters were compared with classifiers containing the clinical parameters alone. An increased C-reactive protein (CRP) value in the final week of radiotherapy was found as a prognostic factor for overall survival, both as a continuous (HR 1.099 (1.038-1.164), p < 0.0012) as well as categorical variable splitting data at the median value of 1.2 mg/dl (HR 2.214 (1.388-3.531), p < 0.0008). In the multivariable analysis, the CRP value-maintained significance with an HR of 1.105 (1.040-1.173) and p-value of 0.0012. The cross validated classifier using CRP at the end of radiotherapy in addition to clinical parameters separated equally sized high and low risk groups more distinctly than a classifier containing the clinical parameters alone (HR = 2.786 (95% CI 1.686-4.605) vs. HR = 2.287 (95% CI 1.407-3.718)). Thus, the CRP value at the end of radiation therapy has successfully passed the crucial cross-validation test. The presented data on CRP levels suggests that inflammatory markers may become increasingly important during definitive radiochemotherapy, particularly with the growing utilization of immunotherapy as a consolidation therapy for stage III NSCLC., (© 2024. The Author(s).)

Background: In patients with oligometastatic NSCLC, a cT3-cT4 primary tumor or an cN2/cN3 lymph node status was reported to be associated with unfavorable outcome. The aim of this study was to assess the importance of definitive or neoadjuvant thoracic radiochemotherapy for long-term outcome of these patients in order to find more appropriate treatment schedules. Methods: Analysis of the West Cancer Centre (WTZ) institutional database from 08/2016 to 08/2020 was performed. Patients with primary synchronous OMD, all without actionable driver mutations, who received definitive thoracic radiochemotherapy (RCT) or neoadjuvant RCT followed by surgery (trimodality treatment) were included. Survival outcome is compared with stage III NSCLC. Results: Altogether, 272 patients received concurrent radiochemotherapy. Of those, 220 presented with stage III (158 with definitive RCT, 62 with trimodality approach). A total of 52 patients had OMD patients with cT3/cT4 or cN2/cN3 tumors. Overall survival (OS) at five years for OMD patients was 28.3% (95%-CI: 16.4-41.5%), which was not significantly different from OS of patients with stage III NSCLC treated with definitive or neoadjuvant RCT (34.9% (95%-CI: 27.4-42.8%)). However, the PFS of OMD patients at five years or last follow-up was significantly worse than that of stage III patients (13.0% vs. 24.3%, p = 0.0048). The latter was due to a higher cumulative incidence of distant metastases in OMD patients (50.2% vs. 20.4% at 48 months, p < 0.0001) in comparison to stage III patients. A cross-validated classifier that included severe comorbidity, ECOG performance status, gender and pre-treatment serum CRP level as the most important factors in the univariable analysis, was able to divide the OMD patient group into two equally sized groups with a four-year survival rate of 49.4% in the good prognosis group and 9.9% in the poor prognosis group ( p = 0.0021). Laboratory chemistry and clinical parameters, in addition to imaging and high-precision therapies, can help to predict and improve prognosis. Conclusions: A multimodality treatment approach and local metastases-directed therapy in addition to chemoimmunotherapy can lead to good long-term survival in patients with cT3/cT4 or cN2/cN3 OMD NSCLC without severe comorbidities and in good performance status and is therefore recommended.

Background: The aim of the present study is to examine the impact of kV-CBCT-based online adaptive radiation therapy (ART) on dosimetric parameters in comparison to image-guided-radiotherapy (IGRT) in consecutive patients with tumors in the head and neck region from a prospective registry., Methods: The study comprises all consecutive patients with tumors in the head and neck area who were treated with kV-CBCT-based online ART or IGRT-modus at the linear-accelerator ETHOS™. As a measure of effectiveness, the equivalent-uniform-dose was calculated for the CTV (EUD CTV ) and organs-at-risk (EUD OAR ) and normalized to the prescribed dose. As an important determinant for the need of ART the interfractional shifts of anatomic landmarks related to the tongue were analyzed and compared to the intrafractional shifts. The latter determine the performance of the adapted dose distribution on the verification CBCT2 postadaptation., Results: Altogether 59 consecutive patients with tumors in the head-and-neck-area were treated from 01.12.2021 to 31.01.2023. Ten of all 59 patients (10/59; 16.9%) received at least one phase within a treatment course with ART. Of 46 fractions in the adaptive mode, irradiation was conducted in 65.2% of fractions with the adaptive-plan, the scheduled-plan in the remaining. The dispersion of the distributions of EUD CTV -values from the 46 dose fractions differed significantly between the scheduled and adaptive plans (Ansari-Bradley-Test, p = 0.0158). Thus, the 2.5th percentile of the EUD CTV -values by the adaptive plans amounted 97.1% (95% CI 96.6-99.5%) and by the scheduled plans 78.1% (95% CI 61.8-88.7%). While the EUD CTV for the accumulated dose distributions stayed above 95% at PTV-margins of ≥ 3 mm for all 8 analyzed treatment phases the scheduled plans did for margins ≥ 5 mm. The intrafractional anatomic shifts of all 8 measured anatomic landmarks were smaller than the interfractional with overall median values of 8.5 mm and 5.5 mm (p < 0.0001 for five and p < 0.05 for all parameters, pairwise comparisons, signed-rank-test). The EUD OAR -values for the larynx and the parotid gland were significantly lower for the adaptive compared with the scheduled plans (Wilcoxon-test, p < 0.001)., Conclusions: The mobile tongue and tongue base showed considerable interfractional variations. While PTV-margins of 5 mm were sufficient for IGRT, ART showed the potential of decreasing PTV-margins and spare dose to the organs-at-risk., (© 2023. The Author(s).)

The aim of this study is to examine the precision of semi-automatic, conventional and automatic volumetry tools for pulmonary nodules in chest CT with phantom N1 LUNGMAN. The phantom is a life-size anatomical chest model with pulmonary nodules representing solid and subsolid metastases. Gross tumor volumes (GTV i s) were contoured using various approaches: manually (0); as a means of semi-automated, conventional contouring with (I) adaptive-brush function; (II) flood-fill function; and (III) image-thresholding function. Furthermore, a deep-learning algorithm for automatic contouring was applied (IV). An intermodality comparison of the above-mentioned strategies for contouring GTV i s was performed. For the mean GTV ref (standard deviation (SD)), the interquartile range (IQR)) was 0.68 mL (0.33; 0.34-1.1). GTV segmentation was distributed as follows: (I) 0.61 mL (0.27; 0.36-0.92); (II) 0.41 mL (0.28; 0.23-0.63); (III) 0.65 mL (0.35; 0.32-0.90); and (IV) 0.61 mL (0.29; 0.33-0.95). GTV ref was found to be significantly correlated with GTV i s (I) p < 0.001, r = 0.989 (III) p = 0.001, r = 0.916, and (IV) p < 0.001, r = 0.986, but not with (II) p = 0.091, r = 0.595. The Sørensen-Dice indices for the semi-automatic tools were 0.74 (I), 0.57 (II) and 0.71 (III). For the semi-automatic, conventional segmentation tools evaluated, the adaptive-brush function (I) performed closest to the reference standard (0). The automatic deep learning tool (IV) showed high performance for auto-segmentation and was close to the reference standard. For high precision radiation therapy, visual control, and, where necessary, manual correction, are mandatory for all evaluated tools.

Interfraction anatomic deformations decrease the precision of radiotherapy, which can be improved by online adaptive radiation therapy (oART). However, oART takes time, allowing intrafractional deformations. In this study on focal radiotherapy for bladder cancer, we analyzed the time effect of oART on the equivalent uniform dose in the CTV (EUD CTV ) per fraction and for the accumulated dose distribution over a treatment series as measure of effectiveness. A time-dependent digital CTV model was built from deformable image registration (DIR) between pre- and post-adaptation imaging. The model was highly dose fraction-specific. Planning target volume (PTV) margins were varied by shrinking the clinical PTV to obtain the margin-specific CTV. The EUD CTV per fraction decreased by-4.4 ± 0.9% of prescribed dose per min in treatment series with a steeper than average time dependency of EUD CTV . The EUD CTV for DIR-based accumulated dose distributions over a treatment series was significantly dependent on adaptation time and PTV margin ( p < 0.0001, Chi2 test for each variable). Increasing adaptation times larger than 10 min by five minutes requires a 1.9 ± 0.24 mm additional margin to maintain EUD CTV for a treatment series. Adaptation time is an important determinant of the precision of oART for one half of the bladder cancer patients, and it should be aimed at to be minimized.

Irradiation with electrons is the primary treatment regime for localized conjunctival low-grade lymphomas. However, radiation-induced cataracts are a major cause of treatment-related morbidity. This study investigates whether lens-sparing electron irradiation produces sufficient disease control rates while preventing cataract formation. All consecutive patients with strictly conjunctival, low-grade Ann Arbor stage IE lymphoma treated with superficial electron irradiation between 1999 and 2021 at our department were reviewed. A total of 56 patients with 65 treated eyes were enrolled with a median follow-up of 65 months. The median dose was 30.96 Gy. A lens-spearing technique featuring a hanging rod blocking the central beam axis was used in 89.2% of all cases. Cumulative incidences of 5- and 10-year infield recurrences were 4.3% and 14.6%, incidences of 5- and 10-year outfield progression were 10.4% and 13.4%. We used patients with involvement of retroorbital structures treated with whole-orbit photon irradiation without lens protection-of which we reported in a previous study-as a control group. The cumulative cataract incidence for patients treated with electrons and lens protection was significantly lower ( p = 0.005) when compared to patients irradiated without lens protection. Thus, electrons are an effective treatment option for conjunctival low-grade lymphomas. The presented lens-sparing technique effectively prevents cataract formation.

Online adaptive radiotherapy (ART) allows adaptation of the dose distribution to the anatomy captured by with pre-adaptation imaging. ART is time-consuming, and thus intra-fractional deformations can occur. This prospective registry study analyzed the effects of intra-fraction deformations of clinical target volume (CTV) on the equivalent uniform dose (EUD CTV ) of focal bladder cancer radiotherapy. Using margins of 5-10 mm around CTV on pre-adaptation imaging, intra-fraction CTV-deformations found in a second imaging study reduced the 10th percentile of EUD CTV values per fraction from 101.1% to 63.2% of the prescribed dose. Dose accumulation across fractions of a series was determined with deformable-image registration and worst-case dose accumulation that maximizes the correlation of cold spots. A strong fractionation effect was demonstrated-the EUD CTV was above 95% and 92.5% as determined by the two abovementioned accumulation methods, respectively, for all series of dose fractions. A comparison of both methods showed that the fractionation effect caused the EUD CTV of a series to be insensitive to EUD CTV -declines per dose fraction, and this could be explained by the small size and spatial variations of cold spots. Therefore, ART for each dose fraction is unnecessary, and selective ART for fractions with large inter-fractional deformations alone is sufficient for maintaining a high EUD CTV for a radiotherapy series.

Neural-network-based outcome predictions may enable further treatment personalization of patients with head and neck cancer. The development of neural networks can prove challenging when a limited number of cases is available. Therefore, we investigated whether multitask learning strategies, implemented through the simultaneous optimization of two distinct outcome objectives (multi-outcome) and combined with a tumor segmentation task, can lead to improved performance of convolutional neural networks (CNNs) and vision transformers (ViTs). Model training was conducted on two distinct multicenter datasets for the endpoints loco-regional control (LRC) and progression-free survival (PFS), respectively. The first dataset consisted of pre-treatment computed tomography (CT) imaging for 290 patients and the second dataset contained combined positron emission tomography (PET)/CT data of 224 patients. Discriminative performance was assessed by the concordance index (C-index). Risk stratification was evaluated using log-rank tests. Across both datasets, CNN and ViT model ensembles achieved similar results. Multitask approaches showed favorable performance in most investigations. Multi-outcome CNN models trained with segmentation loss were identified as the optimal strategy across cohorts. On the PET/CT dataset, an ensemble of multi-outcome CNNs trained with segmentation loss achieved the best discrimination (C-index: 0.29, 95% confidence interval (CI): 0.22-0.36) and successfully stratified patients into groups with low and high risk of disease progression (p=0.003). On the CT dataset, ensembles of multi-outcome CNNs and of single-outcome ViTs trained with segmentation loss performed best (C-index: 0.26 and 0.26, CI: 0.18-0.34 and 0.18-0.35, respectively), both with significant risk stratification for LRC in independent validation (p=0.002 and p=0.011). Further validation of the developed multitask-learning models is planned based on a prospective validation study, which has recently completed recruitment.

Background: While prognosis of glioblastoma after trimodality treatment is well examined, recurrence pattern with respect to the delivered dose distribution is less well described. Therefore, here we examine the gain of additional margins around the resection cavity and gross-residual-tumor., Methods: All recurrent glioblastomas initially treated with radiochemotherapy after neurosurgery were included. The percentage overlap of the recurrence with the gross tumor volume (GTV) expanded by varying margins (10 mm to 20 mm) and with the 95% and 90% isodose was measured. Competing-risks analysis was performed in dependence on recurrence pattern., Results: Expanding the margins from 10 mm to 15 mm, to 20 mm, to the 95%- and 90% isodose of the delivered dose distribution with a median margin of 27 mm did moderately increase the proportion of relative in-field recurrence volume from 64% to 68%, 70%, 88% and 88% ( p < 0.0001). Overall survival of patients with in-and out-field recurrence was similar ( p = 0.7053). The only prognostic factor significantly associated with out-field recurrence was multifocality of recurrence ( p = 0.0037). Cumulative incidences of in-field recurrences at 24 months were 60%, 22% and 11% for recurrences located within a 10 mm margin, outside a 10 mm margin but within the 95% isodose, or outside the 95% isodose ( p < 0.0001). Survival from recurrence was improved after complete resection ( p = 0.0069). Integrating these data into a concurrent-risk model shows that extending margins beyond 10 mm has only small effects on survival hardly detectable by clinical trials., Conclusions: Two-thirds of recurrences were observed within a 10 mm margin around the GTV. Smaller margins reduce normal brain radiation exposure allowing for more extensive salvage radiation therapy options in case of recurrence. Prospective trials using margins smaller than 20 mm around the GTV are warranted.

The risk of overlapping pulmonary toxicity induced by thoracic radio(chemo)therapy and immune checkpoint inhibitor therapy in the treatment of patients suffering from non-small cell lung cancer (NSCLC) is one important challenge in successful radioimmunotherapy. In the present opinion we highlight factors that we find important to be considered before treatment initiation, during the treatment sequence, and after treatment completion combined or sequential application of radio(chemo)therapy and immune checkpoint inhibitor therapy. A major aim is to optimize the therapeutic index and to avoid immune related adverse effects. The goals in the future will be focused not only on identifying patients already in the pretreatment phase who could benefit from this complex treatment, but also in identifying patients, who are most likely to have higher grade toxicity. In this respect, proper assessment of clinical performance status, monitoring for the presence of certain comorbidities, evaluation of laboratory parameters such as TGF-α and IL-6 levels, human leukocyte antigens (HLA), and consideration of other potential biomarkers which will evolve in near future are essential. Likewise, the critical parameters must be monitored during the treatment phase and follow-up care to detect potential side effects in time. With the help of high-end imaging which is already used on a daily basis in image guided radiotherapy (IGRT) for intensity modulated radiotherapy (IMRT), its advanced form volumetric modulated arc therapy (VMAT), and adaptive radiation therapy (ART), clinically relevant changes in lung tissue can be detected at an early stage of disease. Concurrent radiotherapy and immunotherapy requires a special focus on adverse events, particularly of the lung, but, when properly approached and applied, it may offer new perspectives for patients with locally advanced NSCLC to be seriously considered as a curative option., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AstraZeneca- Advisory board function - Research funding to institution, (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Definitive radiochemotherapy (RCT) for non-small cell lung cancer (NSCLC) in UICC/TNM I-IVA (singular, oligometastatic) is one of the treatment methods with a potentially curative concept. However, tumour respiratory motion during RT requires exact pre-planning. There are various techniques of motion management like creating internal target volume (ITV), gating, inspiration breath-hold and tracking. The primary goal is to cover the PTV with the prescribed dose while at the same time maximizing dose reduction of surrounding normal tissues (organs at risk, OAR). In this study, two standardized online breath-controlled application techniques used alternately in our department are compared with respect to lung and heart dose., Materials and Methods: Twenty-four patients who were indicated for thoracic RT received planning CTs in voluntary deep inspiration breath-hold (DIBH) and in free shallow breathing, prospectively gated in expiration (FB-EH). A respiratory gating system by Varian (Real-time Position Management, RPM) was used for monitoring. OAR, GTV, CTV and PTV were contoured on both planning CTs. The PTV margin to the CTV was 5 mm in the axial and 6-8 mm in the cranio-caudal direction. The consistency of the contours was checked by elastic deformation (Varian Eclipse Version 15.5). RT plans were generated and compared in both breathing positions using the same technique, IMRT over fixed irradiation directions or VMAT. The patients were treated in a prospective registry study with the approval of the local ethics committee., Results: The PTV in expiration (FB-EH) was on average significantly smaller than the PTV in inspiration (DIBH): for tumours in the lower lobe (LL) 431.5 vs. 477.6 ml (Wilcoxon test for connected samples; p  = 0.004), in the upper lobe (UL) 659.5 vs. 686.8 ml ( p  = 0.005). The intra-patient comparison of plans in DIBH and FB-EH showed superiority of DIBH for UL-tumours and equality of DIBH and FB-EH for LL-tumours. The dose for OAR in UL-tumours was lower in DIBH than in FB-EH (mean lung dose p  = 0.011; lungV20, p  = 0.002; mean heart dose p  = 0.016). The plans for LL-tumours in FB-EH showed no difference in OAR compared to DIBH (mean lung dose p  = 0.683; V20Gy p  = 0.33; mean heart dose p  = 0.929). The RT setting was controlled online for each fraction and was robustly reproducible in FB-EH., Conclusion: RT plans for treating lung tumours implemented depend on the reproducibility of the DIBH and advantages of the respiratory situation with respect to OAR. The primary tumour localization in UL correlates with advantages of RT in DIBH, compared to FB-EH. For LL-tumours there is no difference between RT in FB-EH and RT in DIBH with respect to heart or lung exposure and therefore, reproducibility is the dominant criterion. FB-EH is recommended as a very robust and efficient technique for LL-tumours., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

We systematically analyzed the kinetics of tumor regression, the impact of residual lesions on disease control and the applicability of the Lugano classification in follow-up MRI of orbital non-Hodgkin lymphomas that were irradiated with photons. We retrospectively analyzed a total of 154 pre- and post-irradiation MRI datasets of 36 patients with low-grade, Ann-Arbor stage I, orbital non-Hodgkin lymphomas. Patients with restricted conjunctival involvement were excluded. Lymphoma lesions were delineated and volumetrically analyzed on T1-weighted sequences. Tumor residues were present in 91.2% of all cases during the first six months after treatment. Volumetric partial response rates (> 50% volume reduction) were 75%, 69.2%, and 50% at 12-24 months, 36-48 months and > 48 months after the end of treatment. The corresponding complete response (CR) rates according to the Lugano classification were 20%, 23.1% and 50%. During a median clinical follow-up of 37 months no significant differences in progression free survival (PFS) rates were observed between the CR and non-CR group (p = 0.915). A residual tumor volume below 20% of the pretreatment volume should be expected at long-term follow-up beyond one year after radiotherapy., (© 2023. The Author(s).)

Background: Computed tomography (CT) studies are requested by specialists from most medical disciplines and play a vital role in the diagnosis and treatment of patients. It follows that physicians of all specialties should possess basic knowledge of computed tomography, its proper use, and the radiation exposure associated with it., Methods: This review is based on publications retrieved by a selective search of the literature., Results: Approximately 12 million CT studies are carried out in Germany each year, and the trend is rising. Approximately 9% of all diagnostic studies involving ionizing radiation are CT studies. On average, more than 60% of the collective effective dose due to medical radiation exposure is attributable to CT. There are two types of radiation effects caused by ionizing radiation: sto - chastic and deterministic. The additional, individual relative lifetime cancer mortality risk due to ionizing radiation with wholebody exposure at a low single dose is estimated at 5% per sievert. Radiation exposure from CT studies of the head and trunk, e.g. of a patient with polytrauma, corresponds to an additional lifetime cancer mortality risk of approximately 0.1% at an effective dose of approximately 20 millisievert., Conclusion: The radiation exposure due to CT, and the risks to which patients are subjected by it, have become more important with greater use of CT. Technical advances, targeted dose monitoring, and analyses of dose data can help identify areas where improvement is necessary, in furtherance of the overriding goal of lowering patients' radiation exposure while preserving adequate image quality.

Importance: Patients with newly diagnosed locally advanced cervical carcinomas or recurrences after surgery undergoing radiochemotherapy whose tumor is unsuited for a brachytherapy boost need high-dose percutaneous radiotherapy with small margins to compensate for clinical target volume deformations and set-up errors. Cone-beam computed tomography-based online adaptive radiotherapy (ART) has the potential to reduce planning target volume (PTV) margins below 5 mm for these tumors., Objective: To compare online ART technologies with image-guided radiotherapy (IGRT) for gynecologic tumors., Design, Setting, and Participants: This comparative effectiveness study comprised all 7 consecutive patients with gynecologic tumors who were treated with ART with artificial intelligence segmentation from January to May 2022 at the West German Cancer Center. All adapted treatment plans were reviewed for the new scenario of organs at risk and target volume. Dose distributions of adapted and scheduled plans optimized on the initial planning computed tomography scan were compared., Exposure: Online ART for gynecologic tumors., Main Outcomes and Measures: Target dose coverage with ART compared with IGRT for PTV margins of 5 mm or less in terms of the generalized equivalent uniform dose (gEUD) without increasing the gEUD for the organs at risk (bladder and rectum)., Results: The first 10 treatment series among 7 patients (mean [SD] age, 65.7 [16.5] years) with gynecologic tumors from a prospective observational trial performed with ART were compared with IGRT. For a clinical PTV margin of 5 mm, IGRT was associated with a median gEUD decrease in the interfractional clinical target volume of -1.5% (90% CI, -31.8% to 2.9%) for all fractions in comparison with the planned dose distribution. Online ART was associated with a decrease of -0.02% (90% CI, -3.2% to 1.5%), which was less than the decrease with IGRT (P < .001). This was not associated with an increase in the gEUD for the bladder or rectum. For a PTV margin of 0 mm, the median gEUD deviation with IGRT was -13.1% (90% CI, -47.9% to 1.6%) compared with 0.1% (90% CI, -2.3% to 6.6%) with ART (P < .001). The benefit associated with ART was larger for a PTV margin of 0 mm than of 5 mm (P = .004) due to spreading of the cold spot at the clinical target volume margin from fraction to fraction with a median SD of 2.4 cm (90% CI, 1.9-3.4 cm) for all patients., Conclusions and Relevance: This study suggests that ART is associated with an improvement in the percentage deviation of gEUD for the interfractional clinical target volume compared with IGRT. As the gain of ART depends on fractionation and PTV margin, a strategy is proposed here to switch from IGRT to ART, if the delivered gEUD distribution becomes unfavorable in comparison with the expected distribution during the course of treatment.

Background: Previous medical history strongly contributes to the genesis of intracranial aneurysms (IA). A possible impact of regular medication on the occurrence of abdominal aortic aneurysms has been reported., Aim: To evaluate the value of regular medication on the risk of development and rupture of IA., Methods: Data on medication use and related comorbidities were obtained from the institutional IA registry. A 1:1 age- and sex-matched patient sample was collected from the population-based Heinz Nixdorf Recall Study with individuals from the same area., Results: In the analysis comparing IA cohort ( n  = 1960) with the matched normal population ( n  = 1960), the use of statins (adjusted odds ratio, 1.34 [95% confidence interval 1.02-1.78]), antidiabetics (1.46 [1.08-1.99]), and calcium channel blockers (1.49 [1.11-2.00]) was independently associated with higher risk of IA, whereas uricostatics (0.23 [0.14-0.38]), aspirin (0.23 [0.13-0.43]), beta-blockers (0.51 [0.40-0.66]), and angiotensin-converting enzyme inhibitors (0.38 [0.27-0.53]) were related to lower risk of IA. In the multivariable analysis within the IA cohort ( n  = 2446), SAH patients showed higher drug exposure with thiazide diuretics (2.11 [1.59-2.80]), but lower prevalence of remaining antihypertensive medication-beta-blockers (0.38 [0.30-0.48]), calcium channel blockers (0.63 [0.48-0.83]), angiotensin-converting enzyme inhibitors (0.56 [0.44-0.72]), and angiotensin-1 receptor blockers (0.33 [0.24-0.45]). Patients with ruptured IA were less likely to be treated with statins (0.62 [0.47-0.81]), thyroid hormones (0.62 [0.48-0.79]), and aspirin (0.55 [0.41-0.75])., Conclusions: Regular medication might impact the risks related to the development and rupture of IA. Further clinical trials are required to clarify the effect of regular medication on IA genesis., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

Purpose: This study aimed to assess interfraction stability of the delivered dose distribution by exhale-gated volumetric modulated arc therapy (VMAT) or intensity-modulated arc therapy (IMAT) for lung cancer and to determine dominant prognostic dosimetric and geometric factors., Methods: Clinical target volume (CTV Plan ) from the planning CT was deformed to the exhale-gated daily CBCT scans to determine CTV i , treated by the respective dose fraction. The equivalent uniform dose of the CTV i was determined by the power law ( g EUD i ) and cell survival model (EUD iSF ) as effectiveness measure for the delivered dose distribution. The following prognostic factors were analyzed: (I) minimum dose within the CTV i (D min&#95;i ), (II) Hausdorff distance (HDD i ) between CTV i and CTV Plan , (III) doses and deformations at the point in CTV Plan at which the global minimum dose over all fractions per patient occurs (PD min&#95;global&#95;i ), and (IV) deformations at the point over all CTV i margins per patient with the largest Hausdorff distance (HDPw orst ). Prognostic value and generalizability of the prognostic factors were examined using cross-validated random forest or multilayer perceptron neural network (MLP) classifiers. Dose accumulation was performed using back deformation of the dose distribution from CTV i to CTV Plan ., Results: Altogether, 218 dose fractions (10 patients) were evaluated. There was a significant interpatient heterogeneity between the distributions of the normalized g EUD i values ( p <0.0001, Kruskal-Wallis tests). Accumulated g EUD over all fractions per patient was 1.004-1.023 times of the prescribed dose. Accumulation led to tolerance of ~20% of fractions with g EUD i < 93% of the prescribed dose. Normalized D min >60% was associated with predicted g EUD values above 95%. D min had the highest importance for predicting the g EUD over all analyzed prognostic parameters by out-of-bag loss reduction using the random forest procedure. Cross-validated random forest classifier based on D min as the sole input had the largest Pearson correlation coefficient (R=0.897) in comparison to classifiers using additional input variables. The neural network performed better than the random forest classifier, and the g EUD values predicted by the MLP classifier with D min as the sole input were correlated with the g EUD values characterized by R=0.933 (95% CI, 0.913-0.948). The performance of the full MLP model with all geometric input parameters was slightly better (R=0.952) than that based on D min ( p =0.0034, Z-test)., Conclusion: Accumulated dose distributions over the treatment series were robust against interfraction CTV deformations using exhale gating and online image guidance. D min was the most important parameter for g EUD prediction for a single fraction. All other parameters did not lead to a markedly improved generalizable prediction. Dosimetric information, especially location and value of D min within the CTV i , are vital information for image-guided radiation treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guberina, Pöttgen, Santiago, Levegrün, Qamhiyeh, Ringbaek, Guberina, Lübcke, Indenkämpen and Stuschke.)

We assessed the long-term outcomes and treatment-related adverse effects of patients with Stage I, "orbital-type" lymphomas that were uniformly treated with photons. All consecutive patients diagnosed with low-grade, Ann Arbor Stage IEA orbital lymphoma treated between 1999 and 2020 at our department were retrospectively reviewed. We excluded patients with exclusive conjunctival involvement, typically treated with en face electrons. In order to quantify radiotherapy related side effects we applied the CTCAE criteria, analyzed changes in visual acuity, quantified dry eye symptoms by use of the Ocular Surface Disease Index (OSDI) score and applied the EORTC QLQ-C30 questionnaire for quality of life (QoL) assessment. In total 66 eyes of 62 patients were irradiated with a median dose of 30.6 Gy. The median follow-up was 43.5 months. The predominant histological subtype were MALT lymphomas. No local failure occurred in this cohort. Of nine outfield relapses, six solely occurred in the contralateral eye. The 5- and 10- years distant progression free survival rates (PFS) were 81.4% and 63.5%. The 5- and 10-years overall survival rates were 85.1% and 71.9% without any tumor related death. Of the acute toxicities none was higher than CTCAE grade 1. The predominant late toxicities were dry eyes (21.2%) of CTCAE Grade <2 and radiation induced cataracts (19.7%). During long-term follow up the average visual acuity did not deteriorate. The global QoL was worst before treatment and improved significantly after 24 months (p = 0.007). External beam radiotherapy of "orbital-type" lymphomas with photons is an effective and gentle treatment option with excellent local control rates. From the high control rates the trend to use slightly lower total doses of 24-27 Gy with conventional fractionation is supported. As non-coplanar radiotherapy techniques improved and total doses can slightly be reduced, the current status of radiotherapy as first line therapy is provided., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Accurate determination of lymph-node (LN) metastases is a prerequisite for high precision radiotherapy. The primary aim is to characterise the performance of PET/CT-based machine-learning classifiers to predict LN-involvement by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in stage-III NSCLC. Prediction models for LN-positivity based on [ 18 F]FDG-PET/CT features were built using logistic regression and machine-learning models random forest (RF) and multilayer perceptron neural network (MLP) for stage-III NSCLC before radiochemotherapy. A total of 675 LN-stations were sampled in 180 patients. The logistic and RF models identified SUV max , the short-axis LN-diameter and the echelon of the considered LN among the most important parameters for EBUS-positivity. Adjusting the sensitivity of machine-learning classifiers to that of the expert-rater of 94.5%, MLP (P = 0.0061) and RF models (P = 0.038) showed lower misclassification rates (MCR) than the standard-report, weighting false positives and false negatives equally. Increasing the sensitivity of classifiers from 94.5 to 99.3% resulted in increase of MCR from 13.3/14.5 to 29.8/34.2% for MLP/RF, respectively. PET/CT-based machine-learning classifiers can achieve a high sensitivity (94.5%) to detect EBUS-positive LNs at a low misclassification rate. As the specificity decreases rapidly above that level, a combined test of a PET/CT-based MLP/RF classifier and EBUS-TBNA is recommended for radiation target volume definition., (© 2022. The Author(s).)

The main objective of this prospective observational study was the characterization of the feasibility and early outcome of image-guided (IG) volumetric modulated arc (VMAT) radiosurgery (SRS) followed by resection for patients with large intraocular melanoma. Our study included consecutive patients with unfavorable-risk melanoma, enrolled in an ophthalmic oncology center. IG-VMAT-SRS was applied by high-resolution 4D image guidance and monitoring. Current stereotactic technique parameters were evaluated for comparison. Side effects and eye function, based on a 5-point CTC assessment score, were quantified. In patients with tumors located more than 0.7-1 mm apart from the optic nerve, partial to complete volume-sparing of the optic nerve head could be achieved. In 95.5% of this subgroup, the vitality of the optic nerve and vision could be preserved by the multimodality-treatment approach (mean follow-up: 18 months (7.5-36 months)). The advanced technology of stereotactic radiotherapy demonstrated the achievability of steep dose gradients around the high-dose volume, with 4D-IG-VMAT dose application. These results enforce IG-VMAT-SRS followed by resection as one of the major therapeutic options for patients with large intraocular melanoma. The combination of 4D-IG high-precision SRS and resection provides an effective treatment for large intraocular melanoma, with few side effects, and enables an eye bulb and even vision preserving modus operandi.

Biliary-tract-carcinomas (BTC), pancreatic-ductal-adenocarcinomas (PDAC) and adenoidcystic-carcinomas (AC) have in common that they are traditionally treated with large clinical-target-volumes (CTV). The aim of this study is to examine the impact of pretreatment-[ 68 Ga]FAPI-PET/CT on target-volume-definition and posttreatment-[ 68 Ga]FAPI-PET/CT-response-assessment for BTC-, PDAC- and AC-patients referred to radiation-therapy. All consecutive BTC-, PDAC-, and AC-patients who received pretreatment-[ 68 Ga]FAPI-PET/CT±[ 18 F]FDG-PET/CT were included from 01.01.2020 to 01.03.2022. MTV and SUV max were separately generated based on [ 68 Ga]FAPI- and [ 18 F]FDG-PET/CT-images. A [ 68 Ga]FAPI- and [ 18 F]FDG-based-CTV was defined. Treatment-plans were compared. Treatment-response was reassessed by a second [ 68 Ga]FAPI-PET/CT and [ 18 F]FDG-PET/CT after treatment-completion. Intermodality comparison of lesion-to-background-ratios [SUV max&#95;lesion /SUV mean&#95;background ] for individual timepoints t 1 and t 2 revealed significant higher values for [ 68 Ga]FAPI compared to [ 18 F]FDG (t 1 , p = 0.008; t 2 , p = 0.005). Intermodality comparison of radiation-therapy-plans showed that [ 68 Ga]FAPI-based planning resulted in D100% = 97.2% and V95% = 98.8% for the [ 18 F]FDG-MTV. [ 18 F]FDG-based-planning resulted in D100% = 35.9% and V95% = 78.1% for [ 68 Ga]FAPI-MTV. [ 18 F]FDG-based-planning resulted only in 2 patients in V95% > 95% for [ 68 Ga]FAPI-MTV, and in 1 patient in D100% > 97% for [ 68 Ga]FAPI-MTV. GTV-coverage in terms of V95% was 76.4% by [ 18 F]FDG-based-planning and 99.5% by [ 68 Ga]FAPI-based-planning. Pretreatment [ 68 Ga]FAPI-PET/CT enhances radiation-treatment-planning in this particular group of patients. While perilesional and tumoral follow-up [ 18 F]FDG-uptake behaved uniformly, perilesional and tumoral reaction may differ in follow-up [ 68 Ga]FAPI-imaging. Complementary [ 68 Ga]FAPI- and [ 18 F]FDG-imaging enhance treatment-response-assessment., (© 2022. The Author(s).)

The pivotal PACIFIC trial defined durvalumab consolidation as the new standard of care in patients with stage III non-small-cell lung cancer treated with definitive radiochemotherapy. The authors characterized the durvalumab effect after induction chemotherapy according to the ESPATUE trial and definitive radiochemotherapy. All consecutive patients with stage III non-small-cell lung cancer receiving definitive radiochemotherapy between January 2017 and February 2020 were included. Primary end points were progression-free survival and overall survival. Altogether, 160 patients (75 PD-L1-positive, 62 PD-L1-negative, 23 unknown) received definitive radiochemotherapy, 146 (91%) of whom received prior induction chemotherapy. Durvalumab consolidation showed high effectiveness overall and in the good-risk group according to the PACIFIC trial (log-rank test: p < 0.005). Hazard ratios for progression-free survival and overall survival were at the lower limits of those in the PACIFIC trial. These results were robust to adjustment for potential confounders by propensity score weighting. Eastern Cooperative Oncology Group (ECOG) performance status was the most important pretreatment prognostic factor.

Abstarct: BACKGROUND: To examine long-term-survival of cT4 cN0/1 cM0 non-small-cell lung carcinoma (NSCLC) patients undergoing definitive radiochemotherapy ( cc RTx/CTx) in comparison to the trimodality treatment, neoadjuvant radiochemotherapy followed by surgery, at a high volume lung cancer center., Methods: All consecutive patients with histopathologically confirmed NSCLC (cT4 cN0/1 cM0) with a curative-intent-to-treat cc RTx/CTx were included between 01.01.2001 and 01.07.2019. Mediastinal involvement was excluded by systematic EBUS-TBNA or mediastinoscopy. Following updated T4-stage-defining-criteria initial staging was reassessed by an expert-radiologist according to UICC-guidelines [8th edition]. Outcomes were compared with previously reported results from patients of the same institution with identical inclusion criteria, who had been treated with neoadjuvant radiochemotherapy and resection. Factors for treatment selection were documented. Endpoints were overall-survival (OS), progression-free-survival (PFS), and cumulative incidences of isolated loco-regional failures, distant metastases, secondary tumors as well as non-cancer deaths within the first year., Results: Altogether 46 consecutive patients with histopathologically confirmed NSCLC cT4 cN0/1 cM0 [cN0 in 34 and cN1 in 12 cases] underwent cc RTx/CTx after induction chemotherapy ( i CTx). Median follow-up was 133 months. OS-rates at 3-, 5-, and 7-years were 74.9%, 57.4%, and 57.4%, respectively. Absolute OS-rate of cc RTx/CTx at 5 years were within 10% of the trimodality treatment reference group (Log-Rank p = 0.184). The cumulative incidence of loco-regional relapse was higher after i CTx +  cc RT/CTx (15.2% vs. 0% at 3 years, p = 0.0012, Gray's test) while non-cancer deaths in the first year were lower than in the trimodality reference group (0% vs 9.1%, p = 0.0360, Gray's test). None of the multiple recorded prognostic parameters were significantly associated with survival after i CTx +  cc RT/CTx: Propensity score weighting for adjustment of prognostic factors between i CTx +  cc RT/CTx and trimodality treatment did not change the results of the comparisons., Conclusions: Patients with cT4 N0/1 M0 NSCLC have comparable OS with cc RTx/CTx and trimodality treatment. Loco-regional relapses were higher and non-cancer related deaths lower with cc RTx/CTx. Definitive radiochemotherapy is an adequate alternative for patients with an increased risk of surgery-related morbidity., (© 2022. The Author(s).)

Background: Radiation exposures from computed tomography (CT) in children are inadequately studied. Diagnostic reference levels (DRLs) can help optimise radiation doses., Objective: To determine local DRLs for paediatric chest CT performed mainly on modern dual-source, multi-slice CT scanners as a function of patient size., Materials and Methods: Five hundred thirty-eight chest CT scans in 345 children under 15 years (y) of age (median age: 8 y, interquartile range [IQR]: 4-13 y) performed on four different CT scanners (38% on third-generation and 43% on second-generation dual-source CT) between November 2013 and December 2020 were retrospectively analysed. Examinations were grouped by water-equivalent diameter as a measure of patient size. DRLs for volume CT dose index (CTDI vol ) and dose-length product (DLP) were determined for six different patient sizes and compared to national and European DRLs., Results: The DRLs for CTDI vol and DLP are determined for each patient size group as a function of water-equivalent diameter as follows: (I) < 13 cm (n = 22; median: age 7 months): 0.4 mGy, 7 mGy·cm; (II) 13 cm to less than 17 cm (n = 151; median: age 3 y): 1.2 mGy, 25 mGy·cm; (III) 17 cm to less than 21 cm (n = 211; median: age 8 y): 1.7 mGy, 44 mGy·cm; (IV) 21 cm to less than 25 cm (n = 97; median: age 14 y): 3.0 mGy, 88 mGy·cm; (V) 25 cm to less than 29 cm (n = 42; median: age 14 y): 4.5 mGy, 135 mGy·cm; (VI) ≥ 29 cm (n = 15; median: age 14 y): 8.0 mGy, 241 mGy·cm. Compared with corresponding age and weight groups, our size-based DRLs for DLP are 54% to 71% lower than national and 23% to 85% lower than European DRLs., Conclusion: We developed DRLs for paediatric chest CT as a function of patient size with substantially lower values than national and European DRLs. Precise knowledge of size-based DRLs may assist other institutions in further dose optimisation in children., (© 2022. The Author(s).)

Background: In the assessment of diseases causing skeletal lesions such as multiple myeloma (MM), whole-body low-dose computed tomography (WBLDCT) is a sensitive diagnostic imaging modality, which has the potential to replace the conventional radiographic survey., Purpose: To optimize radiation protection and examine radiation exposure, and effective and organ doses of WBLDCT using different modern dual-source CT (DSCT) devices, and to establish local diagnostic reference levels (DRL)., Material and Methods: In this retrospective study, 281 WBLDCT scans of 232 patients performed between January 2017 and April 2020 either on a second- (A) or third-generation (B) DSCT device could be included. Radiation exposure indices and organ and effective doses were calculated using a commercially available automated dose-tracking software based on Monte-Carlo simulation techniques., Results: The radiation exposure indices and effective doses were distributed as follows (median, interquartile range): (A) second-generation DSCT: volume-weighted CT dose index (CTDI vol ) 1.78 mGy (1.47-2.17 mGy); dose length product (DLP) 282.8 mGy·cm (224.6-319.4 mGy·cm), effective dose (ED) 1.87 mSv (1.61-2.17 mSv) and (B) third-generation DSCT: CTDI vol 0.56 mGy (0.47-0.67 mGy), DLP 92.0 mGy·cm (73.7-107.6 mGy·cm), ED 0.61 mSv (0.52-0.69 mSv). Radiation exposure indices and effective and organ doses were significantly lower with third-generation DSCT ( P  < 0.001). Local DRLs could be set for CTDI vol at 0.75 mGy and DLP at 120 mGy·cm., Conclusion: Third-generation DSCT requires significantly lower radiation dose for WBLDCT than second-generation DSCT and has an effective dose below reported doses for radiographic skeletal surveys. To ensure radiation protection, DRLs regarding WBLDCT are required, where our locally determined values may help as benchmarks.

Purpose: The aim of this study was to determine local diagnostic reference levels (DRLs) during endovascular diagnostics and therapy of carotid-cavernous fistulas (CCF)., Methods: In a retrospective study design, DRLs, achievable dose (AD) and mean values were assessed for all patients with CCF undergoing diagnostic angiography (I) or embolization (II). All procedures were performed with the flat-panel angiography system Allura Xper (Philips Healthcare). Interventional procedures were differentiated according to the type of CCF and the type of procedure., Results: In total, 86 neurointerventional procedures of 48 patients with CCF were executed between February 2010 and July 2021. The following DRLs, AD and mean values could be determined: (I) DRL 215 Gy ∙ cm 2 , AD 169 Gy ∙ cm 2 , mean 165 Gy ∙ cm 2 ; (II) DRL 350 Gy ∙ cm 2 , AD 226 Gy ∙ cm 2 , mean 266 Gy ∙ cm 2 . Dose levels of embolization were significantly higher compared to diagnostic angiography (p < 0.001). No significant dose difference was observed with respect to the type of fistula or the embolization method., Conclusion: This article reports on diagnostic and therapeutic DRLs in the management of CCF that could serve as a benchmark for the national radiation protection authorities. Differentiation by fistula type or embolization method does not seem to be useful., (© 2021. The Author(s).)

Purpose: This study aims to determine local diagnostic reference levels (DRLs) in the endovascular therapy (EVT) of patients with cranial and spinal dural arteriovenous fistula (dAVF)., Methods: In a retrospective study design, DRLs and achievable dose (AD) were assessed for all patients with cranial and spinal dAVF undergoing EVT (I) or diagnostic angiography (II). All procedures were performed at the flat-panel angiography-system Allura Xper (Philips Healthcare). Interventional procedures were differentiated according to the region of fistula and the type of procedure., Results: In total, 264 neurointerventional procedures of 131 patients with dAVF (94 cranial, 37 spinal) were executed between 02/2010 and 12/2020. The following DRLs, AD, and mean values could be determined: for cranial dAVF (I) DRL 507.33 Gy cm 2 , AD 369.79 Gy cm 2 , mean 396.51 Gy cm 2 ; (II) DRL 256.65 Gy cm 2 , AD 214.19 Gy cm 2 , mean 211.80 Gy cm 2 ; for spinal dAVF (I) DRL 482.72 Gy cm 2 , AD 275.98 Gy cm 2 , mean 347.12 Gy cm 2 ; (II) DRL 396.39 Gy cm 2 , AD 210.57 Gy cm 2 , mean 299.55 Gy cm 2 . Dose levels of EVT were significantly higher compared to diagnostic angiographies (p < 0.001). No statistical difference in dose levels regarding the localization of dAVF was found., Conclusion: Our results could be used for establishing DRLs in the EVT of cranial and spinal dAVF. Because radiation exposure to comparably complex interventions such as AVM embolization is similar, it may be useful to determine general DRLs for both entities together., (© 2021. The Author(s).)

According to a position paper of the European Commission Initiative on Breast Cancer (ECIBC), DBT is close to being introduced in European breast cancer screening programmes. Our study aimed to examine radiation dose delivered by digital breast tomosynthesis (DBT) and digital mammography (FFDM) in comparison to sole FFDM in a clinical follow-up setting and in an identical patient cohort. Retrospectively, 768 breast examinations of 96 patients were included. Patients received both DBT and FFDM between May 2015 and July 2019: (I) FFDM in cranio-caudal (CC) and DBT in mediolateral oblique (MLO) view, as well as a (II) follow-up examination with FFDM in CC and MLO view. The mean glandular dose (MGD) was determined by the mammography system according to Dance's model. The MGD (standard deviation (SD), interquartile range (IQR)) was distributed as follows: (I) (CC FFDM +MLO DBT ) (a) left FFDM CC 1.40 mGy (0.36 mGy, 1.13-1.59 mGy), left DBT MLO 1.62 mGy (0.51 mGy, 1.27-1.82 mGy); (b) right FFDM CC 1.36 mGy (0.34 mGy, 1.14-1.51 mGy), right DBT MLO 1.59 mGy (0.52 mGy, 1.27-1.62 mGy). (II) (CC FFDM +MLO FFDM ) (a) left FFDM CC 1.35 mGy (0.35 mGy, 1.10-1.60 mGy), left FFDM MLO 1.40 mGy (0.39 mGy, 1.12-1.59 mGy), (b) right FFDM CC 1.35 mGy (0.33 mGy, 1.12-1.48 mGy), right FFDM MLO 1.40 mGy (0.36 mGy, 1.14-1.58 mGy). MGD was significantly higher for DBT mlo views compared to FFDM ( p < 0.001). Radiation dose was significantly higher for DBT in MLO views compared to FFDM. However, the MGD of DBT MLO lies below the national diagnostic reference level of 2 mGy for an FFDM view. Hence, our results support the use of either DBT or FFDM as suggested in the ECIBC's Guidelines.

The selective intra-arterial nimodipine application for the treatment of cerebral vasospasm (CVS) in patients after spontaneous subarachnoid hemorrhage (sSAH) is widely employed. The purpose of this study is to examine the radiation exposure and to determine local diagnostic reference levels (DRLs) of intra-arterial nimodipine therapy. In a retrospective study design, DRLs and achievable dose (AD) were assessed for all patients undergoing (I) selective intra-arterial nimodipine application or (II) additional mechanical angioplasty for CVS treatment. Interventional procedures were differentiated according to the type of procedure and the number of probed vessels. Altogether 494 neurointerventional procedures of 121 patients with CVS due to sSAH could be included. The radiation exposure indices were distributed as follows: (I) DRL 74.3 Gy·cm 2 , AD 59.8 Gy·cm 2 ; (II) DRL 128.3 Gy·cm 2 , AD 94.5 Gy·cm 2 . Kruskal-Wallis test confirmed significant dose difference considering the number of probed vessels ( p < 0.001). The mean cumulative dose per patient was 254.9 Gy·cm 2 (interquartile range 88.6-315.6 Gy·cm 2 ). The DRLs of intra-arterial nimodipine therapy are substantially lower compared with DRLs proposed for other therapeutic interventions, such as thrombectomy or aneurysm coiling. However, repeated therapy sessions are often required, bearing the potential risk of a cumulatively higher radiation exposure., (© 2022 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

To compare radiation dose and image quality of three CT-scanners using optimal dose protocols in patients with suspected urolithiasis regarding additional hardware (tin filter) and software (iterative reconstruction). Examinations from a single-source CT-scanner (A2) and a dual-source CT-scanner (DSCT) (A1) were compared to a tin filter DSCT (B) regarding dose-length product (DLP) and volume-weighted CT dose-index (CTDIvol). DLP of B was 51 and 53% lower in comparison to A1 and A2 (78.62, 159.20 and 165.80 mGy·cm, respectively; P < 0.0001). CTDIvol of B was 53% and 56% significantly lower compared to A1 and A2, respectively (1.52 vs. 3.22 vs. 3.46 mGy; P < 0.0001). Image quality in B proved to be similar to A1 and A2 (3.57, 3.51 and 3.60, respectively; P > 0.05). Inter-rater agreement regarding image quality was good for all CT-scanners (κ = 0.62). Modern CTs with a built-in tin filter allow a significant reduction of radiation exposure in patients with suspected urolithiasis by optimizing the X-ray spectrum., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The aim of this study was to investigate the diagnostic accuracy of a radiomics analysis based on a fully automated segmentation and a simplified and robust MR imaging protocol to provide a comprehensive analysis of the genetic profile and grading of cerebral gliomas for everyday clinical use., Methods: MRI examinations of 217 therapy-naïve patients with cerebral gliomas, each comprising a non-contrast T1-weighted, FLAIR and contrast-enhanced T1-weighted sequence, were included in the study. In addition, clinical and laboratory parameters were incorporated into the analysis. The BraTS 2019 pretrained DeepMedic network was used for automated segmentation. The segmentations generated by DeepMedic were evaluated with 200 manual segmentations with a DICE score of 0.8082 ± 0.1321. Subsequently, the radiomics signatures were utilized to predict the genetic profile of ATRX, IDH1/2, MGMT and 1p19q co-deletion, as well as differentiating low-grade glioma from high-grade glioma., Results: The network provided an AUC (validation/test) for the differentiation between low-grade gliomas vs. high-grade gliomas of 0.981 ± 0.015/0.885 ± 0.02. The best results were achieved for the prediction of the ATRX expression loss with AUCs of 0.979 ± 0.028/0.923 ± 0.045, followed by 0.929 ± 0.042/0.861 ± 0.023 for the prediction of IDH1/2. The prediction of 1p19q and MGMT achieved moderate results, with AUCs of 0.999 ± 0.005/0.711 ± 0.128 for 1p19q and 0.854 ± 0.046/0.742 ± 0.050 for MGMT., Conclusion: This fully automated approach utilizing simplified MR protocols to predict the genetic profile and grading of cerebral gliomas provides an easy and efficient method for non-invasive tumor decoding.

The purpose of this study is to examine radiation doses and image quality of a low-dose (LD) protocol for chest and abdomen/pelvis (CAP) CT compared with a standard (STD) protocol. A total of 361 patients were included between October 2019 and April 2020; 104 patients with LD-protocol (100 kV, ref mAs 80 (chest)/145 (abdomen/pelvis)) and 257 patients with STD-protocol (100 kV, ref mAs 100 (chest)/180 (abdomen/pelvis)) at second-generation dual-source CT. Radiation doses for CTDIvol and DLP, and objective and subjective image qualities of 50 examinations from each group were evaluated. The LD-protocol applied significantly lower radiation doses compared with the STD-protocol (p < 0.001), achieving a dose reduction by 37% for the median DLP in chest, 19% in abdomen/pelvis and 22% in total. Median total DLP was 342 mGy·cm (LD) vs. 436 mGy·cm (STD). The LD-CAP CT protocol achieved a significant dose reduction far below national diagnostic reference levels, ensuring acceptable and good image quality., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Multiparametric magnetic resonance imaging (mpMRI) and targeted biopsies (TBs) facilitate accurate detection of significant prostate cancer (sPC). However, it remains unclear how many cores should be applied per target., Objective: To assess sPC detection rates of two different target-dependent magnetic resonance imaging (MRI)/transrectal ultrasonography (TRUS)-fusion biopsy approaches (TB and target saturation [TS]) compared with extended systematic biopsies (SBs)., Design, Setting, and Participants: Retrospective single-centre outcome of transperineal MRI/TRUS-fusion biopsies of 213 men was evaluated. All men underwent TB with a median of four cores per MRI lesion, followed by a median of 24 SBs, performed by experienced urologists. Cancer and sPC (International Society of Urological Pathology grade group ≥2) detection rates were analysed. TB was compared with SB and TS, with nine cores per target, calculated by the Ginsburg scheme and using individual cores of the lesion and its "penumbra"., Outcome Measurements and Statistical Analysis: Cancer detection rates were calculated for TS, TB, and SB at both lesion and patient level. Combination of SB + TB served as a reference. Statistical differences in prostate cancer (PC) detection between groups were calculated using McNemar's tests with confidence intervals., Results and Limitations: TS detected 99% of 134 sPC lesions, which was significantly higher than the detection by TB (87%, p = 0.001) and SB (82%, p < 0.001). SB detected significantly more of the 72 low-risk PC lesions than TB (99% vs 68%, p < 0.001) and 10% (p = 0.15) more than that detected by TS. At a per-patient level, 99% of men harbouring sPC were detected by TS. This was significantly higher than that by TB and SB (89%, p = 0.03 and 81%, p = 0.001, respectively). Limitations include limited generalisability, as a transperineal biopsy route was used., Conclusions: TS detected significantly more cases of sPC than TB and extended SB. Given that both 99% of sPC lesions and men harbouring sPC were identified by TS, the results suggest that this approach allows to omit SB cores without compromising sPC detection., Patient Summary: Target saturation of magnetic resonance imaging-suspicious prostate lesions provides excellent cancer detection and finds fewer low-risk tumours than the current gold standard combination of targeted and systematic biopsies., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

CT myelography (CTM) is a diagnostic technique for the evaluation of various spinal pathologies, and plays an important role in diagnosis of different diseases such as spontaneous intracranial hypotension and postoperative cerebrospinal fluid leaks. The aims of this study were to examine radiation exposure, establish diagnostic reference levels (DRLs) and compare radiation doses of single- and dual-source examinations and different CTM protocols. In this retrospective study, 183 CTMs comprising 155 single-source and 28 dual-source examinations, performed between May 2015 and December 2020, were analyzed. Dose data included 31 whole spine (A), 23 cervical (B), 10 thoracic (C), and 119 lumbar (D) CTMs. Radiation exposure was reported for volume-weighted CT dose index (CTDI vol ) and dose-length product (DLP). Radiation doses for CTDI vol and DLP were distributed as follows (median, IQR): A: 7.44 mGy (6.01-11.17 mGy)/509.7 mGy·cm (382.4-682.9 mGy·cm), B: 9.31 mGy (7.20-14.64 mGy)/214.5 mGy·cm (153.7-308.2 mGy·cm), C: 6.80 mGy (6.14-8.26 mGy)/365.4 mGy·cm (222.8-432.4 mGy·cm), D: 11.02 mGy (7.97-14.89 mGy)/308.0 mGy·cm (224.7-413.7 mGy·cm). Local DRLs could be depicted as follows (CTDI vol /DLP): A: 11 mGy/683 mGy·cm, B: 15 mGy/308 mGy·cm, C: 8 mGy/432 mGy·cm, D: 15 mGy/414 mGy·cm. High image quality was achieved for all anatomical regions. Basically, radiation exposure of CTM differs according to anatomical location.

Purpose: The aim of this study was to compare the pattern of intra-patient spread of lymph-node (LN)-metastases within the mediastinum as assessed by 18 F-FDG PET/CT and systematic endobronchial ultrasound-guided transbronchial-needle aspiration (EBUS-TBNA) for precise target volume definition in stage III NSCLC., Methods: This is a single-center study based on our preceding investigation, including all consecutive patients with initial diagnosis of stage IIIA-C NSCLC, receiving concurrent radiochemotherapy (12/2011-06/2018). Inclusion criteria were curative treatment intent, 18 F-FDG PET/CT and EBUS-TBNA prior to start of treatment. The lymphatic drainage was classified into echelon-1 (ipsilateral hilum), echelon-2 (ipsilateral LN-stations 4 and 7) and echelon-3 (rest of the mediastinum, contralateral hilum). The pattern of spread was classified according to all permutations of echelon-1, echelon-2, and echelon-3 EBUS-TBNA findings., Results: In total, 180 patients were enrolled. Various patterns of LN-spread could be identified. Skip lesions with an involved echelon distal from an uninvolved one were detected in less than 10% of patients by both EBUS-TBNA and PET. The pattern with largest asymmetry was detected in cases with EBUS-TBNA- or PET-positivity at all three echelons (p < 0.0001, exact symmetry test). In a multivariable logistic model for EBUS-positivity at echelon-3, prognostic factors were PET-positivity at echelon-3 (Hazard ratio (HR) = 12.1; 95%-CI: 3.2-46.5), EBUS-TBNA positivity at echelon-2 (HR = 6.7; 95%-CI: 1.31-31.2) and left-sided tumor location (HR = 4.0; 95%-CI: 1.24-13.2). There were significantly less combined ipsilateral upper (LN-stations 2 and 4) and lower (LN-station 7) mediastinal involvements (16.8% of patients) with EBUS-TBNA than with PET (38.9%, p < 0.0001, exact symmetry test). EBUS-TBNA detected a lobe specific heterogeneity between the odds ratios of LN-positivity in the upper versus lower mediastinum (p = 0.0021, Breslow-Day test), while PET did not (p = 0.19)., Conclusion: Frequent patterns of LN-metastatic spread could be defined by EBUS-TBNA and PET and discrepancies in the pattern were seen between both methods. EBUS-TBNA showed more lobe and tumor laterality specific patterns of LN-metastases than PET and skipped lymph node stations were rare. These systematic relations offer the opportunity to further refine multi-parameter risk of LN-involvement models for target volume delineation based on pattern of spread by EBUS-TBNA and PET., (© 2021. The Author(s).)

Purpose: Apart from the commonly applied manual needle biopsy, CT-guided percutaneous biopsies of bone lesions can be performed with battery-powered drill biopsy systems. Due to assumably different radiation doses and procedural durations, the aim of this study is to examine radiation exposure and establish local diagnostic reference levels (DRLs) of CT-guided bone biopsies of different anatomical regions., Methods: In this retrospective study, dose data of 187 patients who underwent CT-guided bone biopsy with a manual or powered drill biopsy system performed at one of three different multi-slice CT were analyzed. Between January 2012 and November 2019, a total of 27 femur (A), 74 ilium (B), 27 sacrum (C), 28 thoracic vertebrae (D) and 31 lumbar vertebrae (E) biopsies were included. Radiation exposure was reported for volume-weighted CT dose index (CTDI vol ) and dose-length product (DLP)., Results: CTDI vol and DLP of manual versus powered drill biopsy were (median, IQR): A: 56.9(41.4-128.5)/66.7(37.6-76.2)mGy, 410(203-683)/303(128-403)mGy·cm, B: 83.5(62.1-128.5)/59.4(46.2-79.8)mGy, 489(322-472)/400(329-695)mGy·cm, C: 97.5(71.6-149.2)/63.1(49.1-83.7)mGy, 627(496-740)/404(316-515)mGy·cm, D: 67.0(40.3-86.6)/39.7(29.9-89.0)mGy, 392(267-596)/207(166-402)mGy·cm and E: 100.1(66.5-162.6)/62.5(48.0-90.0)mGy, 521(385-619)/315(240-452)mGy·cm. Radiation exposure with powered drill was significantly lower for ilium and sacrum, while procedural duration was not increased for any anatomical location. Local DRLs could be depicted as follows (CTDI vol /DLP): A: 91 mGy/522 mGy·cm, B: 90 mGy/530 mGy·cm, C: 116 mGy/740 mGy·cm, D: 87 mGy/578 mGy·cm and E: 115 mGy/546 mGy·cm. The diagnostic yield was 82.4% for manual and 89.4% for powered drill biopsies., Conclusion: Use of powered drill bone biopsy systems for CT-guided percutaneous bone biopsies can significantly reduce the radiation burden compared to manual biopsy for specific anatomical locations such as ilium and sacrum and does not increase radiation dose or procedural duration for any of the investigated locations., Level of Evidence: Level 3., (© 2021. The Author(s).)

Cardiac and liver computed tomography (CT) perfusion has not been routinely implemented in the clinic and requires high radiation doses. The purpose of this study is to examine the radiation exposure and technical settings for cardiac and liver CT perfusion scans at different CT scanners. Two cardiac and three liver CT perfusion protocols were examined with the N1 LUNGMAN phantom at three multi-slice CT scanners: a single-source (I) and second- (II) and third-generation (III) dual-source CT scanners. Radiation doses were reported for the CT dose index (CTDI vol ) and dose-length product (DLP) and a standardised DLP (DLP 10cm ) for cardiac and liver perfusion. The effective dose (ED 10cm ) for a standardised scan length of 10 cm was estimated using conversion factors based on the International Commission on Radiological Protection (ICRP) 110 phantoms and tissue-weighting factors from ICRP 103. The proposed total lifetime attributable risk of developing cancer was determined as a function of organ, age and sex for adults. Radiation exposure for CTDI vol , DLP/DLP 10 cm and ED 10 cm during CT perfusion was distributed as follows: for cardiac perfusion (II) 144 mGy, 1036 mGy·cm/1440 mGy·cm and 39 mSv, and (III) 28 mGy, 295 mGy·cm/279 mGy·cm and 8 mSv; for liver perfusion (I) 225 mGy, 3360 mGy·cm/2249 mGy·cm and 54 mSv, (II) 94 mGy, 1451 mGy·cm/937 mGy·cm and 22 mSv, and (III) 74 mGy, 1096 mGy·cm/739 mGy·cm and 18 mSv. The third-generation dual-source CT scanner applied the lowest doses. Proposed total lifetime attributable risk increased with decreasing age. Even though CT perfusion is a high-dose examination, we observed that new-generation CT scanners could achieve lower doses. There is a strong impact of organ, age and sex on lifetime attributable risk. Further investigations of the feasibility of these perfusion scans are required for clinical implementation., (© 2021 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

PURPOSE/INTRODUCTION: [ 18 F]FDG-PET/CT is the standard imaging-technique for radiation treatment (RT) planning in locally advanced non-small cell lung cancer (NSCLC). The purpose of this study was to examine the additional value of endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) to standard PET/CT for mediastinal lymph-node (LN) staging and its impact on clinical target volume (CTV)., Materials and Methods: All consecutive patients with primary stage III NSCLC who underwent [ 18 F]FDG-PET/CT and EBUS-TBNA prior to RT were analyzed from 12/2011 to 06/2018. LN-stations were assessed by an expert-radiologist and a nuclear medicine-physician. CTV was evaluated by two independent radiation oncologists. LNs were grouped with increasing distance along the lymphatic chains from primary tumor into echelon-1 (ipsilateral hilum), echelon-2 (LN-station 7 and ipsilateral 4), and echelon-3 (remaining mediastinum and contralateral hilum)., Results: A total of 675 LN-stations of which 291 were positive for tumor-cells, were sampled by EBUS-TBNA in 180 patients. The rate of EBUS-positive LNs was 43% among all sampled LNs. EBUS-positivity in EBUS-probed LNs decreased from 85.8% in echelon-1 LNs to 42.4%/ 9.6% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher's exact test). The false discovery rate of PET in comparison with EBUS results rose from 5.3% in echelon-1 to 32.9%/ 69.1% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher's exact test). Sensitivity and specificity of FDG-PET/CT ranged from 85 to 99% and 67 to 80% for the different echelons. In 22.2% patients, EBUS-TBNA finding triggered changes of the treated CTV, compared with contouring algorithms based on FDG-avidity as the sole criterion for inclusion. CTV was enlarged in 6.7% patients due to EBUS-positivity in PET-negative LN-station and reduced in 15.5% by exclusion of an EBUS-negative but PET-positive LN-station., Conclusion: The false discovery rate of [ 18 F]FDG-PET/CT increased markedly with distance from the primary tumor. Inclusion of systematic mediastinal LN mapping by EBUS-TBNA in addition to PET/CT has the potential to increase accuracy of target volume definition, particularly in echelon-3 LNs. EBUS-TBNA is recommended as integral part of staging for radiochemotherapy in stage III NSCLC.

Despite multimodal treatment, the prognosis of patients with glioblastoma (GBM) remains poor. Previous studies showed conflicting results on the effect of antiepileptic drugs (AED) on GBM survival. We investigated the associations of different AED with overall survival (OS) and progression-free survival (PFS) in a large institutional GBM cohort ( n = 872) treated January 2006 and December 2018. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the evidence on the value of AED for GBM prognosis. Of all perioperatively administered AED, only the use of levetiracetam (LEV) was associated with longer OS (median: 12.8 vs. 8.77 months, p < 0.0001) and PFS (7 vs. 4.5 months, p = 0.001). In the multivariable analysis, LEV was independently associated with longer OS (aHR = 0.74, p = 0.017) and PFS (aHR = 0.68, p = 0.008). In the meta-analysis with 5614 patients from the present and seven previously published studies, outcome benefit for OS (HR = 0.83, p = 0.02) and PFS (HR = 0.77, p = 0.02) in GBM individuals with LEV was confirmed. Perioperative treatment with LEV might improve the prognosis of GBM patients. We recommend a prospective randomized controlled trial addressing the efficacy of LEV in GBM treatment.

Background: Fibroblast activation protein (FAP) as a specific marker of activated fibroblasts can be visualized by positron emission tomography (PET) using Ga-68-FAP inhibitors (FAPI). Gallium-68-labeled FAPI is increasingly used in the staging of various cancers. In addition, the first cases of theranostic approaches have been reported. In this work, we describe the phenomenon of myocardial FAPI uptake in patients who received a Ga-68 FAPI PET for tumor staging., Method and Results: Ga-68 FAPI PET examinations for cancer staging were retrospectively analyzed with respect to cardiac tracer uptake. Standardized uptake values (SUV) were correlated to clinical covariates in a univariate regression model. From 09/2018 to 11/2019 N = 32 patients underwent FAPI PET at our institution. Six out of 32 patients (18.8%) demonstrated increased localized myocardial tracer accumulation, with remote FAPI uptake being significantly higher in patients with vs without localized focal myocardial uptake (SUV max 2.2 ± .6 vs 1.5 ± .4, P < .05 and SUV mean 1.6 ± .4 vs 1.2 ± .3, P < .05, respectively). Univariate regression demonstrated a significant correlation of coronary artery disease (CAD), age and left ventricular ejection fraction (LVEF) with remote SUV mean uptake, the latter with a very strong correlation with remote uptake (R 2 = .74, P < .01)., Conclusion: Our study indicates an association of CAD, age, and LVEF with FAPI uptake. Further studies are warranted to assess if fibroblast activation can be reliably measured and may be used for risk stratification regarding early detection or progression of CAD and left ventricular remodeling.

Purpose/Objective(s): The aim of this follow-up analysis of the ESPATUE phase-3 trial was to explore the prognostic value of post-induction chemotherapy PET metrics in patients with stage III non-small cell lung cancer (NSCLC) who were assigned to receive definitive chemoradiotherapy. Materials/Methods: All eligible patients stage IIIA (cN2) and stage IIIB of the trial received induction chemotherapy consisting of 3 cycles of cisplatin/paclitaxel and chemoradiotherapy up to 45 Gy/1.5 Gy per fraction twice-a-day, followed by a radiation-boost with 2 Gy once per day with concurrent cisplatin/vinorelbine. The protocol definition prescribed a total dose of 65-71 Gy. 18 F-FDG-PET/CT (PETpre) was performed at study entry and before concurrent chemoradiotherapy (interim-PET; PETpost). Interim PETpost metrics and known prognostic clinical parameters were correlated in uni- and multivariable survival analyses. Leave-one-out cross-validation was used to show internal validity. Results: Ninety-two patients who underwent 18 F-FDG-PET/CT after induction chemotherapy were enrolled. Median MTVpost value was 5.9 ml. Altogether 85 patients completed the whole chemoradiation with the planned total dose of 60-71 Gy. In univariable proportional hazard analysis, each of the parameters MTVpost, SUV max (post) and TLGmax(post) was associated with overall survival ( P < 0.05). Multivariable survival analysis, including clinical and post-induction PET parameters, found TLGmax(post) (hazard ratio: 1.032 (95%-CI: 1.013-1.052) per 100 ml increase) and total radiation dose (hazard ratio: 0.930 (0.902-0.959) per Gray increase) significantly related with overall survival in the whole group of patients, and also in patients receiving a total dose ≥ 60 Gy. The best leave-one-out cross-validated 2 parameter classifier contained TLGmax(post) and total radiation dose. TLGmax(post) was associated with time to distant metastases ( P = 0.0018), and SUV max (post) with time to loco-regional relapse ( P = 0.039) in multivariable analysis of patients receiving a total dose ≥ 60 Gy. Conclusion: Post-induction chemotherapy PET parameters demonstrated prognostic significance. Therefore, an interim 18 F-FDG-PET/CT is a promising diagnostic modality for guiding individualized treatment intensification., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

The aim of this phantom study is to examine radiation doses of dual- and single-energy computed tomography (DECT and SECT) in the chest and upper abdomen for three different multi-slice CT scanners. A total of 34 CT protocols were examined with the phantom N1 LUNGMAN. Four different CT examination types of different anatomic regions were performed both in single- and dual-energy technique: chest, aorta, pulmonary arteries for suspected pulmonary embolism and liver. Radiation doses were examined for the CT dose index CTDIvol and dose-length product (DLP). Radiation doses of DECT were significantly higher than doses for SECT. In terms of CTDIvol, radiation doses were 1.1-3.2 times higher, and in terms of DLP, these were 1.1-3.8 times higher for DECT compared with SECT. The third-generation dual-source CT applied the lowest dose in 7 of 15 different examination types of different anatomic regions., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Radiation-induced scleral necrosis (RISN) is a rare, but a serious complication of brachytherapy for uveal melanoma. We aimed at analysing the incidence, timing and risk factors associated with development of RISN in a large institutional series., Methods: All consecutive cases with brachytherapy for uveal melanoma treated by the Departments of Ophthalmology and Radiotherapy at University Hospital Essen between 1999 and 2016 were eligible. Development of RISN during the post-treatment follow-up was recorded. A 1:2 propensity score matched case-control study was performed for the evaluation of the prognostic value of different tumour- and treatment-associated parameters., Results: RISN was documented in 115 (2.9%) of 3960 patients with uveal melanoma included in the final analysis, and occurred at the mean 30.3 months (range: 1.26-226 months) after brachytherapy. In the whole cohort, younger age (p = 0.042), plaque type (p = 0.001) and ciliary body involvement (p < 0.0001) were independently associated with the RISN occurrence. In the case-control study, multivariable weighted proportional hazard analysis discovered the association of the following additional tumour- and treatment-associated characteristics with RISN: posterior tumour margin anterior to equatorial region (p = 0.0003), extraocular tumour extension (p = <0.0001), scleral contact dose (p = <0.0001), conjunctival dehiscence after therapy (p = 0.0001), disinsertion of the superior rectus muscle (p = 0.001) and the glaucoma medication (p = 0.014)., Conclusions: Our study confirms RISN as a rare complication, which might occur even years later after the brachytherapy for uveal melanoma. Alongside with scleral dose five other tumour and therapy related factors predict the risk of RISN after brachytherapy for uveal melanoma were established., (© 2021 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To assess suspected acute stroke, the computed tomography (CT) protocol contains a non-contrast CT (NCCT), a CT angiography (CTA), and a CT perfusion (CTP). Due to assumably high radiation doses of the complete protocol, the aim of this study is to examine radiation exposure and to establish diagnostic reference levels (DRLs)., Methods: In this retrospective study, dose data of 921 patients with initial CT imaging for suspected acute stroke and dose monitoring with a DICOM header-based tracking and monitoring software were analyzed. Between June 2017 and January 2020, 1655 CT scans were included, which were performed on three different modern multi-slice CT scanners, including 921 NCCT, 465 CTA, and 269 CTP scans. Radiation exposure was reported for CT dose index (CTDI vol ) and dose-length product (DLP). DRLs were set at the 75th percentile of dose distribution., Results: DRLs were assessed for each step (CTDI vol /DLP): NCCT 33.9 mGy/527.8 mGy cm and CTA 13.7 mGy/478.3 mGy cm. Radiation exposure of CTP was invariable and depended on CT device and its protocol settings with CTDI vol 124.9-258.2 mGy and DLP 1852.6-3044.3 mGy cm., Conclusion: Performing complementary CT techniques such as CTA and CTP for the assessment of acute stroke increases total radiation exposure. Hence, the revised DRLs for the complete protocol are required, where our local DRLs may help as benchmarks.

Purpose: This study aims to determine local diagnostic reference levels (LDRLs) of intra-arterial chemotherapy (IAC) procedures of pediatric patients with retinoblastoma (RB) to provide data for establishing diagnostic reference levels (DRLs) in pediatric interventional radiology (IR)., Methods: In a retrospective study design, LDRLs and achievable dose (AD) were assessed for children undergoing superselective IAC for RB treatment. All procedures were performed at the flat-panel angiography systems (I) ArtisQ biplane (Siemens Healthineers) and (II) Allura Xper (Philips Healthcare). Patients were differentiated according to age (A1: 1-3 months; A2: 4-12 months; A3: 13-72 months; A4: 73 months-10 years; A5: > 10 years), sex, conducted or not-conducted chemotherapy., Results: 248 neurointerventional procedures of 130 pediatric patients (median age 14.5 months, range 5-127 months) with RB (68 unilateral, 62 bilateral) could be included between January 2010 and March 2020. The following diagnostic reference values, AD, and mean values could be determined: (A2) DRL 3.9 Gy cm 2 , AD 2.9 Gy cm 2 , mean 3.5 Gy cm 2 ; (A3) DRL 7.0 Gy cm 2 , AD 4.3 Gy cm 2 , mean 6.0 Gy cm 2 ; (A4) DRL 14.5 Gy cm 2 , AD 10.7 Gy cm 2 , mean 10.8 Gy cm 2 ; (A5) AD 8.8 Gy cm 2 , mean 8.8 Gy cm 2 . Kruskal-Wallis-test confirmed a significant dose difference between the examined age groups (A2-A5) (p < 0.001). There was no statistical difference considering sex (p = 0.076) and conducted or not-conducted chemotherapy (p = 0.627). A successful procedure was achieved in 207/248 cases., Conclusion: We report on radiation exposure during superselective IAC of a pediatric cohort at the German Retinoblastoma Referral Centre. Although an IAC formally represents a therapeutic procedure, our results confirm that radiation exposure lies within the exposure of a diagnostic interventional procedure. DRLs for superselective IAC are substantially lower compared with DRLs of more complex endovascular interventions.

Purpose: To develop and evaluate fully automatic scan range delimitation for chest CT by using deep learning., Materials and Methods: For this retrospective study, scan ranges were annotated by two expert radiologists in consensus in 1149 (mean age, 65 years ± 16 [standard deviation]; 595 male patients) chest CT topograms acquired between March 2002 and February 2019 (350 with pleural effusion, 376 with atelectasis, 409 with neither, 14 with both). A conditional generative adversarial neural network was trained on 1000 randomly selected topograms to generate virtual scan range delimitations. On the remaining 149 topograms the software-based scan delimitations, scan lengths, and estimated radiation exposure were compared with those from clinical routine. For statistical analysis an equivalence test (two one-sided t tests) was used, with equivalence limits of 10 mm., Results: The software-based scan ranges were similar to the radiologists' annotations, with a mean Dice score coefficient of 0.99 ± 0.01 and an absolute difference of 1.8 mm ± 1.9 and 3.3 mm ± 5.6 at the upper and lower boundary, respectively. An equivalence test indicated that both scan range delimitations were similar ( P < .001). The software-based scan delimitation led to shorter scan ranges compared with those used in clinical routine (298.2 mm ± 32.7 vs 327.0 mm ± 42.0; P < .001), resulting in a lower simulated total radiation exposure (3.9 mSv ± 3.0 vs 4.2 mSv ± 3.3; P < .001)., Conclusion: A conditional generative adversarial neural network was capable of automating scan range delimitation with high accuracy, potentially leading to shorter scan times and reduced radiation exposure. Keywords: Adults and Pediatrics, CT, Computer Applications-Detection/Diagnosis, Convolutional Neural Network (CNN), Lung, Radiation Safety, Segmentation, Supervised learning, Thorax © RSNA, 2021 Supplemental material is available for this article., Competing Interests: Disclosures of Conflicts of Interest: A.D. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institution received grant from NVIDIA (graphics card used in this project was part of the "GPU Grant Program" from NVIDIA). The proposed project was and is in no way related to the study. NVIDIA had and has no influence on any part of the study. Other relationships: disclosed no relevant relationships. M.S.K. disclosed no relevant relationships. M.C.S. disclosed no relevant relationships. N.G. disclosed no relevant relationships. L.U. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: institution received grant from Siemens Healthineers and German Cancer Foundation; author received payment for lectures from Bayer Healthcare and Siemens Healthineers. Other relationships: disclosed no relevant relationships. K.N. disclosed no relevant relationships., (2021 by the Radiological Society of North America, Inc.)

Purpose: The aim of the present study based on the PriCoTTF-phase I/II trial is the quantification of skin-normal tissue complication probabilities of patients with newly diagnosed glioblastoma multiforme treated with Tumor Treating Field (TTField) electrodes, concurrent radiotherapy, and temozolomide. Furthermore, the skin-sparing effect by the clinically applied strategy of repetitive transducer array fixation around their center position shall be examined., Material and Methods: Low-dose cone-beam computed tomography (CBCT) scans of all fractions of the first seven patients of the PriCoTTF-phase I/II trial, used for image guidance, were applied for the dosimetric analysis, for precise TTField transducer array positioning and contour delineation. Within this trial, array positioning was varied from fixation-to-fixation period with a standard deviation of 1.1 cm in the direction of the largest variation of positioning and 0.7 cm in the perpendicular direction. Physical TTField electrode composition was examined and a respective Hounsfield Unit attributed to the TTField electrodes. Dose distributions in the planning CT with TTField electrodes in place, as derived from prefraction CBCTs, were calculated and accumulated with the algorithm Acuros XB. Dose-volume histograms were obtained for the first and second 2 mm scalp layer with and without migrating electrodes and compared with those with fixed electrodes in an average position. Skin toxicity was quantified according to Lyman's model. Minimum doses in hot-spots of 0.05 cm 2 and 25 cm 2 ( Δ D 0.05cm 2 , Δ D 25cm 2 ) size in the superficial skin layers were analyzed., Results: Normal tissue complication probabilities (NTCPs) for skin necrosis ranged from 0.005% to 1.474% (median 0.111%) for the different patients without electrodes. NTCP logarithms were significantly dependent on patient (P < 0.0001) and scenario (P < 0.0001) as classification variables. Fixed positioning of TTField arrays increased skin-NTCP by a factor of 5.50 (95%, CI: 3.66-8.27). The variation of array positioning increased skin-NTCP by a factor of only 3.54 (95%, CI: 2.36-5.32) (P < 0.0001, comparison to irradiation without electrodes; P = 0.036, comparison to irradiation with fixed electrodes). NTCP showed a significant rank correlation with D25cm 2 over all patients and scenarios (r s  = 0.76; P < 0.0001)., Conclusion: Skin-NTCP calculation uncovers significant interpatient heterogeneity and may be used to stratify patients into high- and low-risk groups of skin toxicity. Array position variation may mitigate about one-third of the increase in surface dose and skin-NTCP by the TTField electrodes., (© 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)