Predictors of symptomatic intracerebral hemorrhage after endovascular treatment for acute ischemic stroke due to tandem lesion in anterior circulation.

BACKGROUND: Endovascular treatment (EVT) of tandem lesion (TL) in the anterior circulation acute ischemic stroke (IS) usually requires periprocedural antithrombotic treatment and early initiation of dual antiplatelet therapy (DAPT) after carotid stenting. However, it may contribute to an occurrence of symptomatic intracerebral hemorrhage (SICH) in some cases. We investigated factors influencing the SICH occurrence and assessed the possible predictors of SICH after EVT. METHODS: IS patients with TL in the anterior circulation treated with EVT were enrolled in the multicenter retrospective ASCENT study. A good three-month clinical outcome was scored as 0-2 points in modified Rankin Scale (mRS) and recanalization using the TICI scale. SICH was assessed using the SITS-MOST criteria. Logistic regression analysis was used for the assessment of possible predictors of SICH with adjustment for potential confounders. RESULTS: In total, 300 (68.7 % males, mean age 67.3 ± 10.2 years) patients with median of admission NIHSS 17 were analyzed. Recanalization (TICI 2b-3) was achieved in 290 (96.7 %) patients and 176 (58.7 %) had mRS 0-2. SICH occurred in 25 (8.3 %) patients. Patients with SICH did not differ from those without SICH in the rate of periprocedural antithrombotic treatment (64 vs. 57.5 %, p = 0.526) and in the rate of DAPT started within the first 12 h after EVT (20 vs. 42.2 %, p = 0.087). After adjustment, admission NIHSS and admission glycemia were found as the only predictors of SICH after EVT. CONCLUSION: Admission NIHSS and glycemia were found as the only predictors of SICH after EVT for TL. No associations between periprocedural antithrombotic treatment, early start of DAPT after EVT and SICH occurrence were found.

The impact of brain lesions on health-related quality of life in patients with WHO CNS grade 3 or 4 glioma: a lesion-function and resting-state fMRI analysis.

PURPOSE: In glioma patients, tumor development and multimodality therapy are associated with changes in health-related quality of life (HRQoL). It is largely unknown how different types and locations of tumor- and treatment-related brain lesions, as well as their relationship to white matter tracts and functional brain networks, affect HRQoL. METHODS: In 121 patients with pretreated gliomas of WHO CNS grades 3 or 4, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET, resting-state functional MRI (rs-fMRI) and self-reported HRQoL questionnaires (EORTC QLQ-C30/BN20) were obtained. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and lesions with pathologically increased FET uptake were delineated. Effects of tumor lateralization, involvement of white matter tracts or resting-state network nodes by different types of lesions and within-network rs-fMRI connectivity were analyzed in terms of their interaction with HRQoL scores. RESULTS: Right hemisphere gliomas were associated with significantly less favorable outcomes in physical, role, emotional and social functioning, compared with left-sided tumors. Most functional HRQoL scores correlated significantly with right-sided white-matter tracts involvement by T2/FLAIR hyperintensities and with loss of within-network functional connectivity of right-sided nodes. Tumors of the left hemisphere caused significantly more communication deficits. CONCLUSION: In pretreated high-grade gliomas, right hemisphere lesions are associated with reduced HRQoL scores in most functional domains except communication ability, compared to tumors of the left hemisphere. These relationships are mainly observed for T2/FLAIR lesions involving structural and functional networks in the right hemisphere. The data suggest that sparing the right hemisphere from treatment-related tissue damage may improve HRQoL in glioma patients.

Radiomics for the non-invasive prediction of PD-L1 expression in patients with brain metastases secondary to non-small cell lung cancer.

BACKGROUND: The expression level of the programmed cell death ligand 1 (PD-L1) appears to be a predictor for response to immunotherapy using checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC). As differences in terms of PD-L1 expression levels in the extracranial primary tumor and the brain metastases may occur, a reliable method for the non-invasive assessment of the intracranial PD-L1 expression is, therefore of clinical value. Here, we evaluated the potential of radiomics for a non-invasive prediction of PD-L1 expression in patients with brain metastases secondary to NSCLC. PATIENTS AND METHODS: Fifty-three NSCLC patients with brain metastases from two academic neuro-oncological centers (group 1, n = 36 patients; group 2, n = 17 patients) underwent tumor resection with a subsequent immunohistochemical evaluation of the PD-L1 expression. Brain metastases were manually segmented on preoperative T1-weighted contrast-enhanced MRI. Group 1 was used for model training and validation, group 2 for model testing. After image pre-processing and radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. The radiomics model was trained and validated using random stratified cross-validation. Finally, the best-performing radiomics model was applied to the test data. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analyses. RESULTS: An intracranial PD-L1 expression (i.e., staining of at least 1% or more of tumor cells) was present in 18 of 36 patients (50%) in group 1, and 7 of 17 patients (41%) in group 2. Univariate analysis identified the contrast-enhancing tumor volume as a significant predictor for PD-L1 expression (area under the ROC curve (AUC), 0.77). A random forest classifier using a four-parameter radiomics signature, including tumor volume, yielded an AUC of 0.83 ± 0.18 in the training data (group 1), and an AUC of 0.84 in the external test data (group 2). CONCLUSION: The developed radiomics classifiers allows for a non-invasive assessment of the intracranial PD-L1 expression in patients with brain metastases secondary to NSCLC with high accuracy.

Safety and Efficacy of Baseline Antiplatelet Treatment in Patients Undergoing Mechanical Thrombectomy for Ischemic Stroke: Antiplatelets Before Mechanical Thrombectomy.

PURPOSE: To investigate the safety and efficacy of baseline antiplatelet treatment in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). MATERIALS AND METHODS: Baseline use of antiplatelet medication before MT for (AIS) may provide benefit on reperfusion and clinical outcome but could also carry an increased risk of intracranial hemorrhage (ICH). All consecutive patients with AIS and treated with MT with and without intravenous thrombolysis (IVT) between January 2012 and December 2019 in all centers performing MT nationwide were reviewed. Data were prospectively collected in national registries (eg, SITS-TBY and RES-Q). Primary outcome was functional independence (modified Rankin Scale 0-2) at 3 months; secondary outcome was ICH. RESULTS: Of the 4,351 patients who underwent MT, 1,750 (40%) and 666 (15%) were excluded owing to missing data from the functional independence and ICH outcome cohorts, respectively. In the functional independence cohort (n = 2,601), 771 (30%) patients received antiplatelets before MT. Favorable outcome did not differ in any antiplatelet, aspirin, and clopidogrel groups when compared with that in the no-antiplatelet group: odds ratio (OR), 1.00 (95% CI, 0.84-1.20); OR, 1.05 (95% CI, 0.86-1.27); and OR, 0.88 (95% CI, 0.55-1.41), respectively. In the ICH cohort (n = 3,685), 1095 (30%) patients received antiplatelets before MT. The rates of ICH did not increase in any treatment options (any antiplatelet, aspirin, clopidogrel, and dual antiplatelet groups) when compared with those in the no-antiplatelet group: OR, 1.03 (95% CI, 0.87-1.21); OR, 0.99 (95% CI, 0.83-1.18); OR, 1.10 (95% CI, 0.82-1.47); and OR, 1.43 (95% CI, 0.87-2.33), respectively. CONCLUSIONS: Antiplatelet monotherapy before MT did not improve functional independence or increase the risk of ICH.

Impact of prescription isodose level and collimator selection on dose homogeneity and plan quality in robotic radiosurgery.

PURPOSE: In stereotactic radiosurgery (SRS), prescription isodoses and resulting dose homogeneities vary widely across different platforms and clinical entities. Our goal was to investigate the physical limitations of generating dose distributions with an intended level of homogeneity in robotic SRS. METHODS: Treatment plans for non-isocentric irradiation of 4 spherical phantom targets (volume 0.27-7.70 ml) and 4 clinical targets (volume 0.50-5.70 ml) were calculated using Sequential (phantom) or VOLOTM (clinical) optimizers (Accuray, Sunnyvale, CA, USA). Dose conformity, volume of 12 Gy isodose (V12Gy) as a measure for dose gradient, and treatment time were recorded for different prescribed isodose levels (PILs) and collimator settings. In addition, isocentric irradiation of phantom targets was examined, with dose homogeneity modified by using different collimator sizes. RESULTS: Dose conformity was generally high (nCI ≤ 1.25) and varied little with PIL. For all targets and collimator sets, V12Gy was highest for PIL ≥ 80% and lowest for PIL ≤ 65%. The impact of PIL on V12Gy was highest for isocentric irradiation and lowest for clinical targets (VOLOTM optimization). The variability of V12Gy as a function of collimator selection was significantly higher than that of PIL. V12Gy and treatment time were negatively correlated. Plans utilizing a single collimator with a diameter in the range of 70-80% of the target diameter were fastest, but showed the strongest dependence on PIL. CONCLUSION: Inhomogeneous dose distributions with PIL ≤ 70% can be used to minimize dose to normal tissue. PIL ≥ 90% is associated with a marked and significant increase in off-target dose exposure. Careful selection of collimators during planning is even more important.

Recurrent brain metastases: the role of resection of in a comprehensive multidisciplinary treatment setting.

BACKGROUND: Treatment decision for recurrent symptomatic brain metastases (BM) is challenging with scarce data regarding surgical resection. We therefore evaluated the efficacy of surgery for pretreated, recurrent BM in a comprehensive multidisciplinary treatment setting. METHODS: In a retrospective single center study, patients were analyzed, who underwent surgical resection of recurrent BM between 2007 and 2019. Intracranial event-free survival (EFS) and overall survival (OS) were evaluated by Kaplan-Maier and Cox regression analysis. RESULTS: We included 107 patients with different primary tumor entities and individual previous treatment for BM. Primary tumors comprised non-small cell lung cancer (NSCLC) (37.4%), breast cancer (19.6%), melanoma (13.1%), gastro-intestinal cancer (10.3%) and other, rare entities (19.6%). The number of previous treatments of BM ranged from one to four; the adjuvant treatment modalities comprised: none, focal or whole brain radiotherapy, brachytherapy and radiosurgery. The median pre-operative Karnofsky Performance Score (KPS) was 70% (range 40-100) and improved to 80% (range 0-100) after surgery. The complication rate was 26.2% and two patients died during the perioperative period. Sixty-seven (62.6%) patients received postoperative local radio-oncologic and/or systemic therapy. Median postoperative EFS and OS were 7.1 (95%CI 5.8-8.2) and 11.1 (95%CI 8.4-13.6) months, respectively. The clinical status (postoperative KPS ≥ 70 (HR 0.27 95%CI 0.16-0.46; p < 0.001) remained the only independent factor for survival in multivariate analysis. CONCLUSIONS: Surgical resection of recurrent BM may improve the clinical status and thus OS but is associated with a high complication rate; therefore a very careful patient selection is crucial.

Static FET PET radiomics for the differentiation of treatment-related changes from glioma progression.

PURPOSE: To investigate the potential of radiomics applied to static clinical PET data using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine (FET) to differentiate treatment-related changes (TRC) from tumor progression (TP) in patients with gliomas. PATIENTS AND METHODS: One hundred fifty-one (151) patients with histologically confirmed gliomas and post-therapeutic progressive MRI findings according to the response assessment in neuro-oncology criteria underwent a dynamic amino acid PET scan using the tracer O-(2-[18F]fluoroethyl)-L-tyrosine (FET). Thereof, 124 patients were investigated on a stand-alone PET scanner (data used for model development and validation), and 27 patients on a hybrid PET/MRI scanner (data used for model testing). Mean and maximum tumor to brain ratios (TBRmean, TBRmax) were calculated using the PET data from 20 to 40 min after tracer injection. Logistic regression models were evaluated for the FET PET parameters TBRmean, TBRmax, and for radiomics features of the tumor areas as well as combinations thereof to differentiate between TP and TRC. The best performing models in the validation dataset were finally applied to the test dataset. The diagnostic performance was assessed by receiver operating characteristic analysis. RESULTS: Thirty-seven patients (25%) were diagnosed with TRC, and 114 (75%) with TP. The logistic regression model comprising the conventional FET PET parameters TBRmean and TBRmax resulted in an AUC of 0.78 in both the validation (sensitivity, 64%; specificity, 80%) and the test dataset (sensitivity, 64%; specificity, 80%). The model combining the conventional FET PET parameters and two radiomics features yielded the best diagnostic performance in the validation dataset (AUC, 0.92; sensitivity, 91%; specificity, 80%) and demonstrated its generalizability in the independent test dataset (AUC, 0.85; sensitivity, 81%; specificity, 70%). CONCLUSION: The developed radiomics classifier allows the differentiation between TRC and TP in pretreated gliomas based on routinely acquired static FET PET scans with a high diagnostic accuracy.

Radiomics in neuro-oncology: Basics, workflow, and applications.

Over the last years, the amount, variety, and complexity of neuroimaging data acquired in patients with brain tumors for routine clinical purposes and the resulting number of imaging parameters have substantially increased. Consequently, a timely and cost-effective evaluation of imaging data is hardly feasible without the support of methods from the field of artificial intelligence (AI). AI can facilitate and shorten various time-consuming steps in the image processing workflow, e.g., tumor segmentation, thereby optimizing productivity. Besides, the automated and computer-based analysis of imaging data may help to increase data comparability as it is independent of the experience level of the evaluating clinician. Importantly, AI offers the potential to extract new features from the routinely acquired neuroimages of brain tumor patients. In combination with patient data such as survival, molecular markers, or genomics, mathematical models can be generated that allow, for example, the prediction of treatment response or prognosis, as well as the noninvasive assessment of molecular markers. The subdiscipline of AI dealing with the computation, identification, and extraction of image features, as well as the generation of prognostic or predictive mathematical models, is termed radiomics. This review article summarizes the basics, the current workflow, and methods used in radiomics with a focus on feature-based radiomics in neuro-oncology and provides selected examples of its clinical application.

Mechanical Thrombectomy Quality Indicators Study in Czech Stroke Centers: Results of the METRICS Study.

BACKGROUND AND PURPOSE: Rigorous and regular evaluation of defined quality indicators is crucial for further improvement of both technical and clinical results after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Following the recent international multi-society consensus quality indicators, we aimed to assess trend in these indicators on national level. MATERIAL AND METHODS: The prospective multicenter study (METRICS) was conducted in Czech Republic (CR) in year 2019. All participating centers collected technical and clinical data including defined quality indicators and results were subsequently compared with those from year 2016. RESULTS: In the 2019, 1375 MT were performed in the CR and 1178 (86%) patients (50.3% males, mean age 70.5 ± 13.0 years) were analyzed. Recanalization (TICI 2b-3) was achieved in 83.7% of patients and 46.2% of patients had good 3-month clinical outcome. Following time intervals were shortened in comparison to 2016: "hospital arrival - GP" (77 vs. 53 min; p<0.0001), "hospital arrival - maximal achieved recanalization" (122 vs. 93 min; p<0.0001), and "stroke onset - maximal achieved recanalization" (240 vs. 229 min; p p<0.0001). More patients with tandem occlusion were treated in 2019 (7.8 vs. 16.5%; p<0.0001) and more secondary transports were in 2019 (31.3 vs. 37.8%; p=0.002). No difference was found in 3-month clinical outcome and in the rate of periprocedural complications. Results of the METRICS study met all criteria of multi-society consensus quality indicators. CONCLUSION: Nationwide comparison between 2016 and 2019 showed improvement in the key time intervals, but without better overall clinical outcomes after MT.

The economic crisis during the COVID-19 pandemic has a negative effect on tax compliance: Results from a scenario study in Austria.

In a scenario study with 1200 Austrian taxpayers, we examined how tax compliance is affected by the economic crisis related to the COVID-19 pandemic. Moreover, we investigated the potential of trust in government, attitude towards taxes, and justice perceptions in mitigating potential effects. The results suggest a strong effect of the economic environment on tax compliance. Specifically, tax compliance was lower in scenarios where the pandemic had a negative effect on the economy than in scenarios with no negative effect. However, for individuals with a positive attitude towards taxes, compliance was not lower in a negative economic environment than in pre-COVID-19 times. Moreover, we found that taxpayers who were not affected economically, taxpayers with a positive attitude towards taxes, and taxpayers with a low propensity to take risks generally indicated higher levels of tax compliance. Exploratory analyses indicate that taxpayers who change their compliance behavior in response to the economic environment are, on average, younger, less educated, more strongly affected economically, and more uncertain about their current economic situation than taxpayers with stable compliance levels. Policy interventions should target these groups to strengthen tax compliance in times of crisis.

Low risk of contralateral lymph node recurrence in lateralized head and neck carcinoma after postoperative ipsilateral radiotherapy.

PURPOSE: The role of postoperative irradiation to contralateral non-involved neck nodes in lateralized carcinoma of the head and neck is not clear. The contralateral neck failure rate in head and neck carcinoma treated postoperatively with ipsilateral neck irradiation only was evaluated. METHODS: Patients with carcinoma of the oral cavity, oropharynx, or hypopharynx without midline extension treated between 1990 and 2016 were analyzed. After tumor resection and neck dissection (ND), radiotherapy was given to the primary tumor site and ipsilateral neck. High-risk patients additionally received concurrent chemotherapy. Freedom from contralateral neck recurrence (FCNR), locoregional control rate (LRC), overall survival (OS), and disease-free survival (DFS) were evaluated. RESULTS: 197 patients (median age 60.7 years, 66.5% males, 52.8% oropharyngeal carcinomas) were analyzed. Complete resection (R0) was achieved in 85.8% of cases. Ipsilateral ND was performed in all patients and contralateral ND in 144 patients (73.1%). Concurrent chemotherapy was given to 59 patients (30.0%). After a median follow-up of 45.5 months, OS and DFS of all patients were 73.6% and 70.9% at 5 years, respectively. A total of 45 patients (22.8%) suffered from a locoregional recurrence, lymph node metastases of the contralateral neck developed in 12 patients (6.1%) only. There was no significant difference in contralateral nodal failure rate with or without performance of contralateral ND. CONCLUSION: Regional failure of the contralateral neck was low after surgery and ipsilateral neck irradiation in head and neck carcinomas without midline extension, supporting evidence that contralateral neck radiotherapy can safely be omitted in selected cases.

Applications of radiomics and machine learning for radiotherapy of malignant brain tumors.

BACKGROUND: Magnetic resonance imaging (MRI) and amino acid positron-emission tomography (PET) of the brain contain a vast amount of structural and functional information that can be analyzed by machine learning algorithms and radiomics for the use of radiotherapy in patients with malignant brain tumors. METHODS: This study is based on comprehensive literature research on machine learning and radiomics analyses in neuroimaging and their potential application for radiotherapy in patients with malignant glioma or brain metastases. RESULTS: Feature-based radiomics and deep learning-based machine learning methods can be used to improve brain tumor diagnostics and automate various steps of radiotherapy planning. In glioma patients, important applications are the determination of WHO grade and molecular markers for integrated diagnosis in patients not eligible for biopsy or resection, automatic image segmentation for target volume planning, prediction of the location of tumor recurrence, and differentiation of pseudoprogression from actual tumor progression. In patients with brain metastases, radiomics is applied for additional detection of smaller brain metastases, accurate segmentation of multiple larger metastases, prediction of local response after radiosurgery, and differentiation of radiation injury from local brain metastasis relapse. Importantly, high diagnostic accuracies of 80-90% can be achieved by most approaches, despite a large variety in terms of applied imaging techniques and computational methods. CONCLUSION: Clinical application of automated image analyses based on radiomics and artificial intelligence has a great potential for improving radiotherapy in patients with malignant brain tumors. However, a common problem associated with these techniques is the large variability and the lack of standardization of the methods applied.

miR-155 Contributes to Normal Keratinocyte Differentiation and Is Upregulated in the Epidermis of Psoriatic Skin Lesions.

The role of microRNAs (miRNAs) during keratinocyte (KC) differentiation and in skin diseases with epidermal phenotypes has attracted strong interest over the past few years. However, combined mRNA and miRNA expression analyses to elucidate the intricate mRNA-miRNA networks of KCs at different stages of differentiation have not been performed yet. In the present study, we investigated the dynamics of miRNA and mRNA expression during KC differentiation in vitro and in normal and psoriatic epidermis. While we identified comparable numbers of up- and downregulated mRNAs (49% and 51%, respectively), miRNAs were predominantly upregulated (76% vs 24%) during KC differentiation. Further bioinformatics analyses suggested an important inhibitory role for miR-155 in KC differentiation, as it was repressed during KC differentiation in normal skin but strongly upregulated in the epidermis of psoriatic skin lesions. Mimicking the inflammatory milieu of psoriatic skin in vitro, we could show that the pro-inflammatory cytokines IL17, IL1ß and INFγ synergistically upregulated miR-155 expression in KCs. Forced over-expression of miR-155 in human in vitro skin models specifically reduced the expression of loricrin (LOR) in KCs, indicating that miR-155 interferes with the establishment of a normal epidermal barrier. Together, our data indicate that downregulation of miR-155 during KC differentiation is a crucial step for epidermal barrier formation. Furthermore, its strong upregulation in psoriatic lesions suggests a contributing role of miR-155 in the altered keratinocyte differentiation observed in psoriasis. Therefore, miR-155 represents as a potential target for treating psoriatic skin lesions.

Low Levels of Glycemia within the First 48 Hours after Mechanical Thrombectomy for Acute Ischemic Stroke May be Associated with Better Clinical Outcome.

INTRODUCTION: Many different factors may have an impact on clinical outcome after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We aimed to investigate levels of serum glycemia (GLY) within the first 48 hours after MT. SUBJECTS AND METHODS: Consecutive AIS patients were enrolled in the retrospective bi-center study. Neurological deficit was assessed with National Institutes of Health Stroke Scale (NIHSS) and functional outcome after 3 months with modified Rankin scale with a score 0-2 for good outcome. Presence of symptomatic intracerebral hemorrhage was assessed according to the SITS- MOST criteria. RESULTS: In total, 868 patients (442 males, mean age 69.7 ± 12.2 years) with a median of admission NIHSS 17 points were enrolled in the study and 253 (29.1%) of them were diabetics. Recanalization was reached in 758 (87.3%) patients. Patients with good outcome (412, 47.5%) had lower median of GLY (6.5 versus 7.4 mmol/L, P < .0001) within the first 48 hours after MT. Similar results were found also in diabetics (8.1 versus 9.6 mmol/L, P < .0001) and in patients with achieved recanalization (6.5 versus 7.5 mmol/L, P < .0001). Multivariate regression analysis with adjustment for potential confounders showed median of GLY (P = .0001, odds ratio: 0.830, 95% confidence interval: 0.755-0.913) as a predictor of good outcome after MT. CONCLUSION: Lower levels of GLY within the first 48 hours after MT may be associated with better functional outcome after 3 months.

Radiomic analysis of planning computed tomograms for predicting radiation-induced lung injury and outcome in lung cancer patients treated with robotic stereotactic body radiation therapy.

OBJECTIVES: To predict radiation-induced lung injury and outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT) from radiomic features of the primary tumor. METHODS: In all, 110 patients with primary stage I/IIa NSCLC were analyzed for local control (LC), disease-free survival (DFS), overall survival (OS) and development of local lung injury up to fibrosis (LF). First-order (histogram), second-order (GLCM, Gray Level Co-occurrence Matrix) and shape-related radiomic features were determined from the unprocessed or filtered planning CT images of the gross tumor volume (GTV), subjected to LASSO (Least Absolute Shrinkage and Selection Operator) regularization and used to construct continuous and dichotomous risk scores for each endpoint. RESULTS: Continuous scores comprising 1-5 histogram or GLCM features had a significant (p = 0.0001-0.032) impact on all endpoints that was preserved in a multifactorial Cox regression analysis comprising additional clinical and dosimetric factors. At 36 months, LC did not differ between the dichotomous risk groups (93% vs. 85%, HR 0.892, 95%CI 0.222-3.590), while DFS (45% vs. 17%, p < 0.05, HR 0.457, 95%CI 0.240-0.868) and OS (80% vs. 37%, p < 0.001, HR 0.190, 95%CI 0.065-0.556) were significantly lower in the high-risk groups. Also, the frequency of LF differed significantly between the two risk groups (63% vs. 20% at 24 months, p < 0.001, HR 0.158, 95%CI 0.054-0.458). CONCLUSION: Radiomic analysis of the gross tumor volume may help to predict DFS and OS and the development of local lung fibrosis in early stage NSCLC patients treated with stereotactic radiotherapy.

Postoperative local fractionated radiotherapy for resected single brain metastases.

PURPOSE: Evaluation of postoperative fractionated local 3D-conformal radiotherapy (3DRT) of the resection cavity in brain metastases. PATIENTS AND METHODS: Between 2011 and 2016, 57 patients underwent resection of a single, previously untreated (37/57, 65%) or recurrent (20/57, 35%) brain metastasis (median maximal diameter 3.5 cm [1.1-6.5 cm]) followed by 3DRT. For definition of the gross tumor volume (GTV), the resection cavity was used and for the clinical target volume (CTV), margins of 1.0-1.5 cm were added. Median dose was 48.0 Gy (30.0-50.4 Gy) in 25 (10-28) fractions; most patients had 36.0-42.0 Gy in 3.0 Gy fractions (n = 16, EQD210Gy 39.0-45.5 Gy) or 40.0-50.4 Gy in 1.8-2.0 Gy fractions (n = 37, EQD210Gy 39.3-50.0 Gy). RESULTS: Median follow-up was 18 months. Local control rates were 83% at 1 year and 78% at 2 years and were significantly influenced by histology (breast cancer 100%, non-small lung cancer 87%, melanoma 80%, colorectal cancer 26% at 2 years, p = 0.006) and resection status (p < 0.0001), but not by EQD210Gy or size of the planning target volume (median 96.7 ml [16.7-282.8 ml]). At 1 and 2 years, 74% and 52% of the patients were free from distant brain metastases. Salvage procedures were applied in 25/27 (93%) of recurrent patients. Survival was 68% at 1 year and 41% at 2 years and was significantly improved in younger patients (p = 0.006) with higher Karnofsky performance score (p < 0.0001) and without prior radiotherapy (54% vs. 9% at 2 years, p = 0.006). No cases of radiographic or symptomatic radionecrosis were observed. CONCLUSION: Adjuvant fractionated local 3DRT is highly effective in radiosensitive, completely resected metastases and should be considered for treating large resection cavities as an alternative to postoperative stereotactic single dose or hypofractionated radiosurgery.

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer.

PURPOSE: To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients. METHODS: From 2012 to 2016, 106 patients (median age 74 years, range 50-94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent 18F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1-3 cm) in 86 patients (81%) and IIA (T2a/b, 3-5 cm) in 20 patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5 Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%. RESULTS: Median follow-up was 15 months (range 0.5-46 months). Acute side effects were mild (fatigue grade 1-2 in 20% and dyspnea grade 1-2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80-96%) at 2 years and 77% (95%CI 56-98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23-31 months). Overall survival was 77% (95%CI 65-85%) at 2 years and 56% (95%CI 39-73%) at 3 years. CONCLUSION: CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

The effect of oxytocin on group formation and strategic thinking in men.

Decision-making in groups is a remarkable and decisive element of human societies. Humans are able to organize themselves in groups, engage in collaborative decision-making processes and arrive at a binding agreement, even in the absence of unanimous consent. However, the transfer of decision-making autonomy requires a willingness to deliberately expose oneself to the decisions of others. A lack of trust in the abilities of others or of the underlying decision-making process, i.e. public trust, can lead to a breakdown of organizations in political or economic domains. Recent studies indicate that the biological basis of trust on an individual level is related to Oxytocin, an endogenous neuropeptide and hormone, which is also associated with pro-social behavior and positive conflict resolution. However, little is known about the effects of Oxytocin on the inclination of individuals to form or join groups and to deliberately engage in collaborative decision-making processes. Here, we show that intranasal administration of Oxytocin (n = 60) compared to placebo (n = 60) in males causes an adverse effect on the choice for forming groups in the presence of a competitive environment. In particular, Oxytocin negatively affects the willingness to work collaboratively in a p-Beauty contest game, whereas the effect is most pronounced for participants with relatively high strategic sophistication. Since our data provide initial evidence that Oxytocin has a positive effect on strategic thinking and performance in the p-Beauty contest game, we argue that the adverse effect on group formation might be rooted in an enhanced strategic sophistication of participants treated with Oxytocin.

Clinical routine assessment of palliative care symptoms and concerns and caregiver burden in glioblastoma patients: an explorative field study.

The implementation of self-reported outcome measurements into clinical routine was tested to help facilitate early access to palliative care (PC) for glioblastoma (GBM)-patients. Measures detail PC symptoms and concerns and caregiver burden. Between January 2014 and December 2016, a total of 337 GBM-patients were discussed during meetings of the neuro-oncology tumor board to examine further treatment options. Each patient, along with their caregivers, was requested to participate in self-assessment using the palliative outcome scale (POS) and the Zarit Burden Interview (ZBI). Analyses encompassed summary statistics, non-parametric tests, visual graphic analysis, content analysis and assessing the utilization of the specialized PC consulting service (SPCCS). Ninety-five (28%) GBM-patients and 71 (21%) caregivers completed the self-assessment. Of these, 20 patients and 12 caregivers repeated the assessment at least once more during follow-up. POS total scores were similar in the group of patients with initial diagnosis [10 (0-31)] and those with later disease stages like recurrent diagnosis [9 (0-25)], but ZBI total scores differed [14 (0-51) vs. 24 (2-62)]. Single item analysis demonstrated that anxiety and worries about the future predominated. Caregivers were torn between high engagement in caring and feeling overburdened. Still, requests for the SPCCS showed no increase. Actual implementation of measures like POS and ZBI for detecting PC concerns and caregiver burden with GBM-patients in the field remains challenging as indicated by the limited response rate and lack of increased requests for the SPCCS. Modified clinical routines including strengthening awareness of PC, and allowing proxy-assessment might help to overcome barriers.

Radiomics derived from amino-acid PET and conventional MRI in patients with high-grade gliomas.

Radiomics is a technique that uses high-throughput computing to extract quantitative features from tomographic medical images such as MRI and PET that usually are beyond visual perception. Importantly, the radiomics approach can be performed using neuroimages that have already been acquired during the routine follow-up of the patients allowing an additional data evaluation at low cost. In Neuro-Oncology, these features can potentially be used for differential diagnosis of newly diagnosed cerebral lesions suggestive for brain tumors or for the prediction of response to a neurooncological treatment option. Furthermore, especially in the light of the recent update of the World Health Organization classification of brain tumors, radiomics also has the potential to non-invasively assess important prognostic and predictive molecular markers such as a mutation in the isocitrate dehydrogenase gene or a 1p/19q codeletion which are not accessible by conventional visual interpretation of MRI or PET findings. This review summarizes the current status of the rapidly evolving field of radiomics with a special focus on patients with high-grade gliomas.