This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Introduction:The German Hodgkin Study Group (GHSG) HD17 trial established the omission of radiotherapy (RT) for patients with early-stage unfavorable Hodgkin lymphoma being PET-negative after 2 cycles of BEACOPP escalated plus 2 cycles of ABVD. This patient group reveals heterogeneity in characteristics and disease extent which prompted us to perform a decisive dosimetric analysis according to GHSG risk factors. This may help to tailor RT individually balancing risks and benefits.Methods:For quality assurance, RT-plans were requested from the treating facilities (n= 141) and analyzed centrally. Dose-volume histograms were scanned either paper-based or digitally to obtain doses to mediastinal organs. These were registered and compared according to GHSG risk factors.Results:Overall, RT plans of 176 patients were requested, 139 of which had dosimetric information on target volumes within the mediastinum. Most of these patients were stage II (92.8%), had no B-symptoms (79.1%) and were aged < 50 years (89.9%). Risk factors were present in 8.6% (extranodal involvement), 31.7% (bulky disease), 46.0% (elevated erythrocyte sedimentation rate) and 64.0% (three involved areas), respectively. The presence of bulky disease significantly affected the mean RT doses to the heart (p=0.005) and to the left lung (median: 11.3 Gy vs. 9.9 Gy; p=0.042) as well as V5 of the right and left lung, respectively (median right lung: 67.4% vs. 51.0%; p=0.011; median left lung: 65.9% vs. 54.2%; p=0.008). Significant differences in similar organs at risk parameters could be found between the sub-cohorts with the presence or absence of extranodal involvement, respectively. In contrast, an elevated erythrocyte sedimentation rate did not deteriorate dosimetry significantly. No association of any risk factor with radiation doses to the female breast was found.Conclusion:Pre-chemotherapy risk factors may help to predict potential RT exposure to normal organs and to critically review treatment indication. Individualized risk-benefit evaluations for patients with HL in early-stage unfavorable disease are mandatory.

Purpose: Radiation therapy (RT) is an integral part of treatment concepts for early-stage Hodgkin lymphoma. This analysis reports on RT quality in the recent HD16 and 17 trials of the German Hodgkin Study Group (GHSG).Methods and Materials: All RT plans of involved-node radiation therapy (INRT) in HD 17 were requested for analysis, along with 100 and 50 involved -field radiation therapy (IFRT) plans in HD 16 and 17, respectively. A structured assessment regarding field design and protocol adherence was performed by the reference radiation oncology panel of the GHSG.Results: Overall, 100 (HD 16) and 176 (HD 17) patients were eligible for analysis. In HD 16, 84% of RT series were evaluated as correct, with significant improvement compared with the predecessor studies (P < .001). In HD 17, 76.1% of INRT cases revealed a correct RT design compared with 69.0% of IFRT-cases, which was superior to previous studies (P < .001). Comparing INRT and IFRT, we found no significant differences in the percentage of any deviation (P = .418) or major deviations (P = .466). Regarding dosimetry, INRT was accompanied by an improvement in thyroid doses. Comparing different RT techniques, we found that intensity-modulated RT showed a reduction of high doses in the lung at the expense of an increased low-dose exposure in HD 17.Conclusions: The latest study generation of the GHSG demonstrates an improved quality in RT. A modern INRT design could be established without deterioration in quality. On a conceptual level, an individual consideration of the appropriate RT technique has to be performed.(c) 2022 The Author(s). Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Children between 1.5 and 4 years old were tested for their ability to relocate a hidden object after a 180° self-produced movement around an array of four locations. In one task the object′s location relative to the other locations could be uniquely defined within one dimension, while in another two dimensions were needed to do this. No differences emerged between conditions, and by 3 years few errors occurred, despite the fact that children were unable to view the array during movement. This indicates either that young children encounter no specific difficulty in coordinating dimensions or that they solved the task without recourse to such a system. An error analysis supports the second possibility. Children apparently tackled the task by a system directly related to body movement, since errors were frequently the result of incomplete compensation for movement around the array. In a second study in which the four containers were placed in contact, children′s performance declined and the relation between direction of movement and error was replaced by some evidence for updating on the near-far dimension accompanied by failure to update the left-right dimension. Thus children appear to change strategy when the problem requires more precise specification of target location.

Table 1: Size of the planning targe volume (PTV) and dose exposure to organs at risks in comparison between involved-field (IFRT) radiotherapy and involved-node radiotherapy (INRT). Gy: Gray Question: The HD17 trial of the German Hodgkin Study Group evaluated the value of consolidative involved-node (IN)RT for patients with PET-positivity after chemotherapy and enabled a comparison between INRT and involved-field (IF)RT [1]. The present work analyzes the organs at risk (OAR) exposure of the performed RT. Methods/Material: For dosimetric evaluation, all INRT-plans in the HD 17 trial were requested and compared to a random selection of IFRT-cases in the standard arm. Dose-volume histograms (DVH), either paper-based or digital, were analyzed using SPSS (version 28, IBM, Armonk, NY, USA). For comparisons between the two RT concepts, a two-sided t-test or a Mann-Whitney U test was used with a p-value < 0.05 considered as significant. Results: In total, 148 DVH (INRT: 112, IFRT: 36) could be evaluated. Details on planning target volume (PTV) size and OAR exposure are shown in table 1. The introduction of INRT decreased the PTV size without reaching statistical significance. There was a consistent decrease in OAR-doses with INRT except for V5 in both lungs and V10 and Dmean in the right lung. Despite the dosimetric advantages, significant differences in favor of INRT could only be found for the spinal cord and thyroid. Conclusion: INRT, in comparison to IFRT, decreases PTV-size and OAR exposure and may help to comply with modern dose constraints [2]. Literature 1. Lancet Oncol. 2021 Feb;22(2):223-234. 2. Blood. 2019 Mar 21;133(12):1384-1385.

Question: The HD 16 trial of the German Hodgkin Study Group (GHSG) investigated the use of consolidative radiotherapy (RT) after 2 cycles of ABVD chemotherapy for early-stage Hodgkin lymphoma (HL) and could demonstrate the superiority of a combined modality approach [1]. The present work aims at analyzing the quality of involved-field RT used in this study. Methods/Material: For quality assessment, 100 randomly chosen plans from the HD 16 trial were requested and analyzed. RT was assessed by experts of the radiation therapy panel of the GHSG using initial (staging) imaging, RT plans and the recommendation forms by the reference radiation oncology. Evaluation was graded as „correct“, „minor deviation“ or „major deviation“. Statistical analyses were performed using SPSS (version 27/28, IBM, NY, USA). Results: Radiation doses were adequate with a median of 20 Gy (19.8 Gy-21.6 Gy) in normofractionation. In the majority of radiation series, supradiaphragmatic target volumes were treated (91 %), with the regions most commonly irradiated being supraclavicular left/right (73 % each), infraclavicular left/right (73 % each) and cervical left/right (44 % and 45 %, respectively). Acute treatment toxicities were mild to moderate with only 3 cases of grade 3–4 toxicities (1 nausea/vomiting, 1 dysphagia, 1 mucositis). According to the RT panel, 84 % of cases were evaluated as „correct“, 5 % as „minor deviations“ and 11 % as „major deviations“. Major deviations were caused by insufficient dose coverage of involved regions in most cases (10/11), predominantly in the upper mediastinum (5/10 cases). Previous GHSG studies in early-stage HL (HD 10 [2] and HD 13 [3]) showed lower rates of RT series according to protocol (38.8 % and 52 %, respectively). A χ2-test was used to compare the number of correct RT series in the different GHSG study generations (HD 13 vs. HD 16). No expected cell frequencies were below 5. Results reveal a significant improvement in favor of HD 16 (χ2(1)=33.8, p<0.001 Φ=-0.247). Similar outcomes were found for the association of GHSG study generation and the absence of major deviations (χ2(1)=27.4, p<0.001 Φ=- 0.222). Conclusion: Since its introduction in HD10, involved-field RT has evolved considerably. However, continuous efforts in RT quality assurance and training are needed in the modern era. Literature 1.JCO. November 2019; 37(31):2835-2845. 2.IJROBP. August 2008; 71 (5):1419-1424. 3.SUON. February 2017;193(2):109-115.

Question: The use of radiotherapy (RT) for intermediate-stage Hodgkin lymphoma is discussed vividly. The HD17 trial of the German Hodgkin Study Group (GHSG) evaluated the value of consolidative involved-node (IN)RT for patients with PET-positivity after chemotherapy and enabled a comparison between INRT and involved-field (IF)RT [1]. The present work analyzes the quality of the performed RT. Methods/Material: For quality assessment, all INRT-plans in the HD 17 trial were requested and compared to a random selection of IFRT-cases in the standard arm. The RT was assessed by experts of the radiation therapy panel of the GHSG using initial (staging) imaging, RT plans and the recommendation forms by the reference radiation oncology. Evaluation was graded as „correct“, „minor deviation“ or „major deviation“. Statistical analyses were per-formed using a chi-square test in SPSS (version 27/28, IBM, NY, USA). Results: In total, 178 patients (INRT: 136, IFRT: 42) were analyzed, treated with a median RT dose of 30 Gy (IFRT: 18–30.6 Gy, INRT: 14 Gy-40 Gy). The majority (76.5 %) of INRT-cases showed no deviation compared to 69.1 % of IFRT-cases. Deviations were reported for 9.6 % and 14.0 % of patients in the INRT-group compared to 11.9 % and 19.1 % in the IFRT-group for minor and major deviations, respectively. There was no significant difference between both cohorts regarding the percentage of plans with deviations (p=0.333) or the percentage of major deviations (p=0.423). The principal causes for major deviations were too narrow target volumens in the involved region (IFRT: 6 vs. INRT: 1) or incorrect RT doses (IFRT: 1, INRT: 2). Conclusion: The performed INRT was delineated and planned correctly in most cases and reveals a high degree of quality. There has been no decline in RT-planning in comparison to IFRT. Continuous education is pivotal to enable high-quality INRT outside of clinical trials. Literature 1.Lancet Oncol. 2021 Feb;22(2):223-234.

Hintergrund: Die SARS-CoV-2 ("severe acute respiratory syndrome coronavirus 2") Pandemie stellt sowohl national als auch global alle Gesundheitssysteme vor neuen bisher so noch nie dagewesenen Herausforderungen für die

Overall survival (OS) of patients with brain metastases treated with hypofractionated (HFSRT) or single-fraction (SRS) radiosurgery depends on several prognostic factors. The aim of this study was to investigate the potential of sex as an independent predictor of OS and evaluate the predictive accuracy of common prognostic scores. Retrospective analysis of 281 consecutive patients receiving radiosurgery of brain metastases was performed. Kaplan–Meier survival curves and Cox proportional hazards models were used to compare OS between SRS and HFSRT and by sex, before and after propensity-score matching (PSM) on key baseline prognostic covariates. Prognostic scores were evaluated using Harrell’s concordance index. Median OS was 11 months after both SRS and HFSRT. After PSM, median OS was 12 months after SRS (95% CI: 7.5–16.5) and 9 months after HFSRT (95% CI: 5.0–13.0; p = 0.77). Independent prognostic factors were sex, primary tumor, KPI, and systemic disease status. Median OS was 16 months for women and 7 months for male patients ( p < 0.001). After excluding sex specific tumors, PSM revealed a median OS of 16 months for women and 8 months for male patients ( p < 0.01). Evaluation of prognostic indices showed BSBM to be the most accurate (Harrell’s C = 0.68), followed by SIR (0.61), GPA (0.60), RPA (0.58), and Rades et al. (0.57). OS after HFSRT and SRS did not differ, although PSM revealed a non-significant advantage for SRS. Female sex was found to be a major independent positive prognostic factor for survival, and thus should be considered in the personalized decision-making of brain metastases treatment.

Electric cell-substrate impedance spectroscopy (ECIS) enables non-invasive and continuous read-out of electrical parameters of living tissue. The aim of the current study was to investigate the performance of interdigitated sensors with 50 μm electrode width and 50 μm inter-electrode distance made of gold, aluminium, and titanium for monitoring the barrier properties of epithelial cells in tissue culture. At first, the measurement performance of the photolithographic fabricated sensors was characterized by defined reference electrolytes. The sensors were used to monitor the electrical properties of two adherent epithelial barrier tissue models: renal proximal tubular LLC-PK1 cells, representing a normal functional transporting epithelium, and human cervical cancer-derived HeLa cells, forming non-transporting cancerous epithelial tissue. Then, the impedance spectra obtained were analysed by numerically fitting the parameters of the two different models to the measured impedance spectrum. Aluminium sensors proved to be as sensitive and consistent in repeated online-recordings for continuous cell growth and differentiation monitoring as sensors made of gold, the standard electrode material. Titanium electrodes exhibited an elevated intrinsic ohmic resistance in comparison to gold reflecting its lower electric conductivity. Analysis of impedance spectra through applying models and numerical data fitting enabled the detailed investigation of the development and properties of a functional transporting epithelial tissue using either gold or aluminium sensors. The result of the data obtained, supports the consideration of aluminium and titanium sensor materials as potential alternatives to gold sensors for advanced application of ECIS spectroscopy.

Abstract Background The present study investigates the intrafractional accuracy of a frameless thermoplastic mask used for head immobilization during stereotactic radiotherapy. Non-invasive masks cannot completely prohibit head movements. Previous studies attempted to estimate the magnitude of intrafractional inaccuracy by means of pre- and postfractional measurements only. However, this might not be sufficient to accurately map also intrafractional head movements. Materials and methods Intrafractional deviation of mask-fixed head positions was measured in five patients during a total of 94 fractions by means of close-meshed repeated ExacTrac measurements (every 1.4 min) conducted during the entire treatment session. A median of six (range: 4 to 11) measurements were recorded per fraction, delivering a dataset of 453 measurements. Results Random errors (SD) for the x, y and z axes were 0.27 mm, 0.29 mm and 0.29 mm, respectively. Median 3D deviation was 0.29 mm. Of all 3D intrafractional motions, 5.5 and 0.4% exceeded 1 mm and 2 mm, respectively. A moderate correlation between treatment duration and mean 3D displacement was determined (rs = 0.45). Mean 3D deviation increased from 0.21 mm (SD = 0.26 mm) in the first 2 min to a maximum of 0.53 mm (SD = 0.31 mm) after 10 min of treatment time. Conclusion Pre- and post-treatment measurement is not sufficient to adequately determine the range of intrafractional head motion. Thermoplastic masks provide both reliable interfractional and intrafractional immobilization for image-guided stereotactic hypofractionated radiotherapy. Greater positioning accuracy may be obtained by reducing treatment duration (< 6 min) and applying intrafractional correction. Trial registration Clinicaltrials.gov, NCT03896555, Registered 01 April 2019 - retrospectively registered.

AIM:of this study is to determine the temporal resolution of therapy-induced pneumonitis, and to assess promoting factors in adjuvant treated patients with unilateral mammacarcinoma. PATIENTS AND METHODS:A total of 100 post-surgery patients were recruited. The cohort was treated by 2 field radiotherapy (2FRT; breast and chest wall, N = 75), 3 field radiotherapy (3FRT; + supraclavicular lymphatic region, N = 8), or with 4 field radiotherapy (4FRT; + parasternal lymphatic region, N = 17). Ninety-one patients received various systemic treatments prior to irradiation. Following an initial screening visit post-RT, two additional visits after 12 and 25 weeks were conducted including radiographic examination. In addition, general anamnesis and the co-medication were recorded. The endpoint was reached as soon as a pneumonitis was developed or at maximum of six months post-treatment. RESULTS:A pneumonitis incidence of 13% was determined. Of 91 patients with prior systemic therapy, 11 patients developed pneumonitis. Smoking history and chronic obstructive pulmonary disease (COPD) appeared to be positive predictors, whereas past pneumonia clearly promoted pneumonitis. Further pneumonitis-promoting predictors are represented by the applied field extensions (2 field radiotherapy [2FRT] < 3 field radiotherapy [3FRT] < 4 field radiotherapy [4FRT]) and the type of combined initial systemic therapies. As a consequence, all of the three patients in the study cohort treated with 4FRT and initial chemotherapy combined with anti-hormone and antibody protocols developed pneumonitis. A combination of the hormone antagonists tamoxifen and goserelin might enhance the risk for pneumonitis. Remarkably, none of the 11 patients co-medicated with statins suffered from pneumonitis. CONCLUSIONS:The rapidly increasing use of novel systemic therapy schedules combined with radiotherapy (RT) needs more prospective studies with larger cohorts. Our results indicate that contribution to pneumonitis occurrence of various (neo)adjuvant therapy approaches followed by RT is of minor relevance, whereas mean total lung doses of >10 Gy escalate the risk of lung tissue complications. The validity of potential inhibitors of therapy-induced pneumonitis as observed for statin co-medication should further be investigated in future trials.

A comprehensive evaluation of the current national and regional radiotherapy capacity in Austria with an estimation of demands for 2020 and 2030 was performed by the Austrian Society for Radiation Oncology, Radiobiology and Medical Radiophysics (ÖGRO).

In recent decades, targeted therapeutics have significantly improved therapy results in patients with malignant tumors of different origins. However, malignant diseases characterized by aggressiveness and increased capacity for metastatic spread still require basic researchers and clinicians to direct enormous efforts toward the development of novel therapeutic targets. Potential targets should be selected with the clinical endpoint in view; targeted therapeutics can be developed: for use in combination with currently existing therapeutic approaches in order to improve their efficacy; to overcome the treatment resistance of tumor cells and thus protect the patient from recurrence; to repress molecular mechanisms related to immune escape of cancer cells; and to combat the metastatic dissemination of carcinoma cells. Taking into account the specific clinical aim that should be achieved, different strategies and techniques can be proposed to identify the most promising candidate molecules for further development as therapeutic targets. Since cellular membranes contain a large number of druggable molecules, evaluation of the membrane protein profiles of carcinoma cells having different properties can provide a basis for further development of therapeutic targets. This review considers how cellular membranes obtained from different pre-clinical and clinical samples can be used in screening and to identify targets for cancer therapy.

A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC).

Background. Radiation therapy (RT) of the head and neck region is often accompanied by serious side effects. Research in this area is needed to improve treatment outcomes and ameliorate therapy tolerance. Laboratory rodents are barely matching today's clinical standards in RT research. Yet domestic swine (Sus scrofa domestica) have previously proved suitable for various advanced tests in clinical research and training. We therefore investigated whether S. scrofa domestica is also appropriate for irradiation of the mandible.Study Design. A common scheme for irradiation treatment of S. scrofa domestica mandibles in a split-mouth design was acquired by applying computed tomography (CT) scanning under sedation. Basing on close anatomic resemblance, a standard treatment plan comprising 2 opposed irradiation fields could be accomplished.Results. RT was carried out in a clinical environment with 2 x 9 Gy. The resulting operating procedure facilitated complication-free sedation, transport, positioning, CT scanning, and effective irradiation.Conclusion. Based on common standards applied for RT in humans, domestic pigs can be employed to progress RT clinical research. Due to their human-like anatomy, physiology, size, and weight, the swine model is expedient for advancing experimental RT of the head and neck area.

Studies in human patients and animals have revealed sex-specific differences in susceptibility to renal diseases. Because actions of female sex hormones on normal renal tissue might protect against damage, we searched for potential influences of the female hormone cycle on basic renal functions by studying excretion of urinary marker proteins in healthy human probands. We collected second morning spot urine samples of unmedicated naturally ovulating women, postmenopausal women, and men daily and determined urinary excretion of the renal tubular enzymes fructose-1,6-bisphosphatase and glutathione-S-transferase-α Additionally, we quantified urinary excretion of blood plasma proteins α1-microglobulin, albumin, and IgG. Naturally cycling women showed prominent peaks in the temporal pattern of urinary fructose-1,6-bisphosphatase and glutathione-S-transferase-α release exclusively within 7 days after ovulation or onset of menses. In contrast, postmenopausal women and men showed consistently low levels of urinary fructose-1,6-bisphosphatase excretion over comparable periods. We did not detect changes in urinary α1-microglobulin, albumin, or IgG excretion. Results of this study indicate that proximal tubular tissue architecture, representing a nonreproductive organ-derived epithelium, undergoes periodical adaptations phased by the female reproductive hormone cycle. The temporally delimited higher rate of enzymuria in ovulating women might be a sign of recurring increases of tubular cell turnover that potentially provide enhanced repair capacity and thus, higher resistance to renal damage.

The majority of tumor-related deaths are due to metastasis. Despite the clinical importance of understanding metastasis, we lack knowledge of the molecular mechanisms underlying tumor cell spreading and cell survival far from the primary tumor. Elucidating the molecular characteristics of highly metastatic carcinoma cells would help identify biomarkers or therapeutic targets relevant to predicting or combatting metastasis, and for this the phenotype of metastatic cells could be much more important than their genotype. Hence, proteomic approaches have wide potential utility. This review discusses possibilities of analyzing metastasis-specific protein patterns in a range of sample types, including in vitro and in vivo cancer models, and tissues and biological fluids from patients. Proteome approaches can identify proteins involved in regulating the metastatic capacities of tumors.