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Background: Metastatic castration-resistant prostate cancer poses a therapeutic challenge with poor prognosis. The VISION trial showed prolonged progression-free and overall survival in patients treated with lutetium Lu 177 vipivotide tetraxetan (177Lu-PSMA-617) radioligand therapy compared with using the standard of care (SoC) alone. The objective of this study was to determine the cost-effectiveness of 177Lu-PSMA-617 treatment compared with SoC therapy. Methods: A partitioned survival model was developed using data from the VISION trial, which included overall and progression-free survival and treatment regimens for 177Lu-PSMA-617 and SoC. Treatment costs, utilities for health states, and adverse events were derived from public databases and the literature. Because 177Lu-PSMA-617 was only recently approved, costs for treatment were extrapolated from 177Lu-DOTATATE. Outcome measurements included the incremental cost, effectiveness, and cost-effectiveness ratio. The analysis was performed in a US setting from a healthcare system perspective over the lifetime horizon of 60 months. The willingness-to-pay threshold was set to $50,000, $100,000, and $200,000 per quality-adjusted life years (QALYs). Results: The 177Lu-PSMA-617 group was estimated to gain 0.42 incremental QALYs. Treatment using 177Lu-PSMA-617 led to an increase in costs compared with SoC ($169,110 vs $85,398). The incremental cost, effectiveness, and cost-effectiveness ratio for 177Lu-PSMA-617 therapy was $200,708/QALYs. Sensitivity analysis showed robustness of the model regarding various parameters, which remained cost-effective at all lower and upper parameter bounds. In probabilistic sensitivity analysis using Monte Carlo simulation with 10,000 iterations, therapy using 177Lu-PSMA-617 was determined as the cost-effective strategy in 37.14% of all iterations at a willingness-to-pay threshold of $200,000/QALYs. Conclusions: Treatment using 177Lu-PSMA-617 was estimated to add a notable clinical benefit over SoC alone. Based on the model results, radioligand therapy represents a treatment strategy for patients with metastatic castration-resistant prostate cancer with cost-effectiveness in certain scenarios.

Chimeric antigen receptor T-cell (CAR-T) therapy is associated with a distinct toxicity profile that includes cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS is characterized by the release of pro-inflammatory cytokines such as interleukin 6 (IL-6) and is closely linked to CAR-T expansion and bystander cells like monocytes/macrophages. In other hyperinflammatory states, obesity contributes to inflammatory cascades and acts as a risk factor for disease severity. We aimed to study the influence of anthropometric and body composition (BC) measurements on CAR-T-related immunotoxicity in 64 patients receiving CD19-directed CAR-T for relapsed/refractory Bcell malignancies. Patients with grade ≥2 CRS presented with a significantly higher median body mass index (BMI), waist circumference, waist-to-height ratio (WtHR) and visceral adipose tissue (VAT). These parameters were also found to be associated with an earlier CRS onset. Other adipose deposits and muscle mass did not differ between patients with grade 0-1 CRS versus grade ≥2 CRS. Moreover, BC parameters did not influence ICANS severity or onset. In a multivariate binary logistic regression incorporating known risk factors of immunotoxicity, the factors BMI, waist circumference, WtHR and VAT increased the probability of grade ≥2 CRS. Receiver operating characteristic analyses were utilized to determine optimal discriminatory thresholds for these parameters. Patients above these thresholds displayed markedly increased peak IL-6 levels. Our data imply that increased body composition and VAT in particular represent an additional risk factor for severe and early CRS. These findings carry implications for risk-stratification prior to CD19 CAR-T and may be integrated into established risk models.

Background CD19. CAR T-cells for the treatment of relapsed and refractory (r/r) Diffuse Large B-Cell Lymphoma (DLBCL) demonstrated complete responses in 40%-58% of the patients. Recently, others could associate high tumor volume and low CAR T-cell expansion in vivo with poor outcome. We hypothesize, that the expansion and immunphenotype of (CAR) T cells in vivo determine treatment response and depend on patient- and disease associated factors. Materials and Methods Patients with r/r DLBCL (n=34) were treated with either Axi-cel or Tisa-cel at the University Hospitals of Erlangen and Munich (LMU). The CAR T-cell product and peripheral blood were collected on day 0, 4, 7, 14, 30, 60 and 90 post transfusion. CAR T-cells were detected through flow cytometry utilizing a two step-staining with a biotinylated CD19 protein. Effector:Target (E:T) Ratios were estimated as absolute peak expansion of CAR T-cells (/ul) per tumorvolume (cm3). Responder (R, complete or partial remission) were compared to Non-Responder (NR, stable or progressive disease) according to response assessment with PET-CT three months after transfusion. Results CAR T-cell expansion peaked between day 7 and day 14 after transfusion with a greater expansion of CD8+compared to CD8- CAR T-cells on day 14 (59.27% vs 37.42%, p=0.021). The ratio of CD8+ and CD8- CAR T-cells did not differ between R and NR, however R exhibited higher E:T ratios of CD3+ CAR T-cells compared to NR (20.94 vs 12.81, p=0.015) and an increased E:T ratio of CD8+ CAR T-cells correlated with better progression-free survival (p=0.033). Interestingly, high CRP and ferritin levels at baseline were inversely associated with the E:T ratio (p=0.048 and p=0.017). CD3+ CAR T-cells of R showed earlier peak expression of PD-1 than NR (day 7 vs day 21). Further, peak expansion of CD3+ CAR T-cells correlated with higher PD-1 expression in R but not in NR (p=0.003 vs p=0.12). In addition, R revealed an increased relative frequency of effector memory differentiated CD3+ CAR T-cells (CCR7-CD45RA-, p=0.02), whereas CAR T-cells in NR showed an increased relative frequency of a naive phenotype (CCR7+CD45RA+, p=0.001) on day 7 post infusion. Conclusions Flow-based immunomonitoring with longitudinal characterization of CAR T-cells demonstrated a correlation of the E:T ratio with treatment response and survival. Increased inflammatory conditions at baseline correlated with diminished E:T ratios. Notably, in R CAR peak expansion was positively associated with higher PD-1 expression suggestive for superior CAR T-cell activation. In addition, greater memory differentiation was associated with efficacy during the time of peak expansion. Multiparameter analysis with other clinical covariates will show, whether CAR T-cell expansion and immunphenotypes can predict patient outcome. Disclosure Information V. Blumenberg: B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Significant; Novartis, Gilead Sciences, Janssen, BMS/Celgene. S. Volkl: None. G. Busch: None. S. Baumann: None. M. Winkelmann: None. B. Tast: None. D. Nixdorf: None. G. Hanel: None. L. Frolich: None. C. Schmidt: None. R. Jitschin: None. F. Vettermann: None. W. Kunz: None. D. Mougiakakos: None. M. von Bergwelt: None. V. Bucklein: None. A. Mackensen: None. M. Subklewe: None.

Objectives Abbreviated breast MRI (AB-MRI) was introduced to reduce both examination and image reading times and to improve cost-effectiveness of breast cancer screening. The aim of this model-based economic study was to analyze the cost-effectiveness of full protocol breast MRI (FB-MRI) vs. AB-MRI in screening women with dense breast tissue for breast cancer. Methods Decision analysis and a Markov model were designed to model the cumulative costs and effects of biennial screening in terms of quality-adjusted life years (QALYs) from a US healthcare system perspective. Model input parameters for a cohort of women with dense breast tissue were adopted from recent literature. The impact of varying AB-MRI costs per examination as well as specificity on the resulting cost-effectiveness was modeled within deterministic sensitivity analyses. Results At an assumed cost per examination of $ 263 for AB-MRI (84% of the cost of a FB-MRI examination), the discounted cumulative costs of both MR-based strategies accounted comparably. Reducing the costs of AB-MRI below $ 259 (82% of the cost of a FB-MRI examination, respectively), the incremental cost-effectiveness ratio of FB-MRI exceeded the willingness to pay threshold and the AB-MRI-strategy should be considered preferable in terms of cost-effectiveness. Conclusions Our preliminary findings indicate that AB-MRI may be considered cost-effective compared to FB-MRI for screening women with dense breast tissue for breast cancer, as long as the costs per examination do not exceed 82% of the cost of a FB-MRI examination. Key Points • Cost-effectiveness of abbreviated breast MRI is affected by reductions in specificity and resulting false positive findings and increased recall rates. • Abbreviated breast MRI may be cost-effective up to a cost per examination of 82% of the cost of a full protocol examination. • Abbreviated breast MRI could be an economically preferable alternative to full protocol breast MRI in screening women with dense breast tissue.

The unprecedented demand for hospital services during the SARS-CoV-2 (COVID-19) pandemic has dramatically reduced the capability for dealing with non-acute health needs, including cancer care [1, 2]. To alleviate burden on health care systems, including imaging and laboratory services, curtailment of non-COVID-19-related research activity has been necessary [3]. Measures that reduce hospital visits have been adopted to limit risk of infection and death, which is critical in a cancer population whose age and immunocompromised status increases their risk [4]. Imaging, however, requires hospital visits and close contact with staff and equipment; both are sources of disease transmission. Equipment used to image COVID-19 cases may retain virus on its surface for days [5, 6] unless disinfected. The need for social distancing and for disinfecting equipment substantially slows imaging workflow and reduces throughput. This article discusses the specific impact of pandemics such as SARS-CoV-2 on imaging in oncological trials.

BACKGROUND AND PURPOSE: The role of collateral imaging in selecting patients for endovascular thrombectomy beyond 6 hours from onset has not been established. To assess the comparative utility of collateral imaging using multiphase CTA in selecting late window patients for EVT. MATERIALS AND METHODS: We used data from a prospective multicenter observational study in which all patients underwent imaging with multiphase CT angiography as well as CTP. Two blinded reviewers evaluated patients’ eligibility for endovascular thrombectomy using published collateral imaging (multiphase CTA) criteria compared with CTP using the selection criteria of the Clinical Mismatch in the Triage of Wake Up and Late Presenting Strokes Undergoing Neurointervention with Trevo (DAWN) and Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3 (DEFUSE-3) trials. CTP images were processed using automated commercial software. The outcomes of patients eligible for endovascular thrombectomy according to multiphase CTA, DAWN, or DEFUSE-3 criteria were compared using multivariable logistic regression modeling. Model characteristics were compared using the C-statistic for the receiver operating characteristic curve, the Akaike information criterion, and the Bayesian information criterion. RESULTS: Eighty-six patients presented beyond 6 hours from onset/last known well (median, 9.6 hours; interquartile range, 4.1 hours). Thirty-five patients (40.7%) received endovascular thrombectomy, of whom good functional outcome (90-day mRS, 0–2) was achieved in 16/35 (47%). Collateral-based imaging paradigms significantly modified the treatment effect of endovascular thrombectomy on 90-day mRS 0–2 (Pinteraction = .007). The multiphase CTA–based regression model best fit the data for the 90-day outcome (C-statistic, 0.86; 95% CI, 0.77–0.94) and was associated with the least information loss (Akaike information criterion, 95.7; Bayesian information criterion, 114.9) compared with CTP-based models. CONCLUSIONS: The collateral-based imaging paradigm using multiphase CTA compares well with CTP in selecting patients for endovascular thrombectomy in the late time window.

Background and purpose Acute ischemic stroke treatment with intravenous thrombolysis (IVT) is restricted to a time window of 4.5 h after known or presumed onset. Recently, magnetic resonance imaging-guided treatment decision-making in wake-up stroke (WUS) was shown to be effective. The aim of this study was to determine the safety and outcome of IVT in patients with a time window beyond 4.5 h selected by computed tomography perfusion (CTP) imaging. Methods We analyzed all consecutive patients last seen well beyond 4.5 h after stroke onset treated with IVT based on CTP between January 2015 and October 2018. CTP was visually assessed to estimate the mismatch between cerebral blood flow and cerebral blood volume maps. Early infarct signs were documented according to Alberta Stroke Program Early CT Score (ASPECTS). Safety data were obtained for mortality and symptomatic intracerebral hemorrhage (sICH). Follow-up was assessed with the modified Rankin Scale (mRS). Results A total of 70 patients fulfilled the inclusion criteria (mean age ± SD 77.6 ± 11.5 years, 50.0% female). Median National Institutes of Health Stroke Scale score on admission was 8.0 [interquartile range (IQR), 4-14]. The most frequent reasons for an extended time window were WUS (60.0%) and delayed hospital admission (27.1%). Median time from last seen well to IVT was 11.4 h. Median ASPECTS was 10 (IQR, 9-10) and CTP mismatch 90% (IQR, 80%-100%). A total of 24 patients (34.3%) underwent additional mechanical thrombectomy. sICH occurred in four patients (5.7%). At follow-up, 49.3% had an mRS score of 0-2 and 22.4% had an mRS score of 0-1. Conclusions In patients presenting in an extended time window beyond 4.5 h, IVT treatment with decision-making based on CTP might be a safe procedure. Further evaluation in clinical trials is needed.

Clinical background If pheochromocytoma (PC) or paraganglioma (PGL) is diagnosed based on serologic studies, imaging is required to locate the adrenal mass for further management. Besides pathognomonic hormonal findings, PC/PGL can exhibit typical imaging features. However, PC/PGL can also show morphological overlap with other pathologies. Standard radiological methods The modality of choice for evaluation of PC is CT. In case of extra-adrenal location, MRI is superior to CT. Imaging with PET-CT provides complementary information in the differentiation of PC/PGL and is recommended as the imaging modality of choice for malignant PC/PGL. 68Ga-DOTATATE (or 68Ga-DOTATOC/ 68Ga-DOTANOC) PET-CT has high sensitivity for SDHx-mutated PC/PGL and serves for planning of radioreceptor therapy with somatostatin analogues. In contrast, 123I-metaiodobenzylguanidine (MIBG) scintigraphy is important in assessing the potential efficacy of radioreceptor therapy with MIBG. Methodical details The CT protocol for PC evaluation should include non-enhanced, arterial, portal-venous and late phases; the latter for the evaluation of wash-out. Recent studies indicate non-enhanced CT alone may be sufficient to rule out PC. For MRI, in- and opposed-phase sequences should be additionally acquired. Practical recommendations A relevant proportion of PC is diagnosed incidentally. Therefore, imaging of PC will gain further importance. Recent studies show better response rates of PC/PGL after radioreceptor therapy with somatostatin analogues (177Lu-DOTATATE) than with MIBG. Therefore, 68Ga-DOTATATE PET-CT gains further importance-for diagnostic imaging and therapy planning.

Imaging is crucial for management of patients with possible cerebral venous thrombosis (CVT). To evaluate the cost-effectiveness of different noninvasive imaging strategies in patients with possible CVT. A decision model based on Markov simulations estimated lifetime costs and quality-adjusted life years (QALY) associated with the following imaging strategies: non-contrast CT (NCCT), NCCT plus CT venography (CTV), routine MRI without vascular imaging (R-MRI), and MRI with venography (MRV). The analysis was performed from a US healthcare perspective. Model input was based on best available and most recent evidence, including outcome data from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Starting age was 37 years; both high and low pre-test probabilities of CVT were evaluated. Probabilistic sensitivity analyses (PSA) estimated model uncertainty. In the base-case analysis, NCCT and CTV were dominant over R-MRI and MRV. CTV led to incremental lifetime QALYs compared with NCCT (23.385 QALYs vs. 23.374 QALYs) at slightly higher lifetime costs ($5210 vs. $5057). In PSA, CTV was the strategy with the highest percentage of cost-effective iterations if willingness-to-pay (WTP) thresholds were higher than $13,750/QALY. Complying with contemporary WTP thresholds, CTV was thus identified as the most cost-effective strategy. When the pre-test probability was set to 50%, CTV was also preferred. In patients at the peak age of CVT incidence yet low clinical pre-test probability, diagnostic imaging with CTV is the most cost-effective strategy.

Mit der zunehmenden Inzidenz der Vulva- und Vaginalkarzinome ist auch mit einer zunehmenden Bedeutung der Systemtherapie bei fortgeschrittenen und metastasierten Tumoren zu rechnen. In den einschlagigen Leitlinien wird der Einsatz bei mangelhafter Datenlage zuruckhaltend bewertet. Die vorliegenden Daten aus der Literatur zur Systemtherapie (ohne Radiochemotherapie) sollen dargestellt werden und auf ihre Anwendbarkeit im Einzelfall in den verschiedenen Therapiesituationen Neoadjuvanz, Adjuvanz und Palliation gewertet werden. Es wurde eine Literaturrecherche in PubMed mit den Schlagwortern „vulvar cancer“ und „systemic therapy“ oder „systemic treatment“ oder „chemotherapy“ oder „neoadjuvant chemotherapy“ sowie „vaginal cancer“ und „systemic treatment“ oder „chemotherapy“ oder „neoadjuvant chemotherapy“ von Januar 1990 bis Juli 2018 durchgefuhrt. Die Daten beschranken sich im Wesentlichen auf retrospektive, einarmige, monozentrische Untersuchungen an meist sehr kleinen Fallzahlen, bestenfalls handelt es sich um prospektive multizentrische Phase-II-Studien. Als Orientierung konnen die bei den haufigeren, biologisch ahnlichen Entitaten Zervixkarzinom und Analkarzinom verwendeten Zytostatika und -kombinationen dienen. Bei jungeren Patientinnen mit HPV(humanes Papillomvirus)-induzierten Vulva- und Vaginalkarzinomen ist mit einer besseren Wirksamkeit und Vertraglichkeit der Chemotherapie zu rechnen. Erste Ergebnisse zu zielgerichteten Therapien deuten auf eine Wirksamkeit von EGFR(„epidermal growth factor receptor“)-gerichteten Therapien. Insbesondere bei HPV-induzierten Tumoren konnte die Krebsimmuntherapie zukunftig eine Option sein. Aufgrund der sparlichen Daten ist ein Einsatz von Systemtherapien auf Einzelfalle zu beschranken, bei denen es um eine Reduzierung von Folgen anderer Therapiemodalitaten gehen muss oder andere Behandlungsoptionen nicht (mehr) zur Verfugung stehen. Die Seltenheit dieser Tumoren macht internationale Studienkooperationen und Registerstudien zur Erfassung der Therapierealitat erforderlich. Eine Chance ist moglicherweise die Ubertragbarkeit von Ergebnissen bei haufigeren Tumorentitaten mit ahnlichen biologischen Eigenschaften und Ansatzen fur zielgerichtete Therapien.

Stroke is the most common cause of disability in high-income countries. Several countries offer a limited range of advanced treatments with implications for outcomes, disability and costs. This study estimates the burden of disability that could have been avoided through the transition from traditional (no intravenous thrombolytic therapy (IVT), or endovascular thrombectomy (EVT)) to modern stroke treatments (treatment in stroke units, IVT and EVT). We perform a cost-effectiveness analysis comparing best practice with traditional stroke care, using Greece as a case study.A Markov model was used to calculate costs and Quality Adjusted Life Years (QALYs) for each treatment strategy, using a lifetime horizon. Data for model inputs were derived from meta-analyses of trials, and national and international cost databases. Sensitivity analyses were also performed to address potential uncertainty and test the robustness of the findings.Incremental effectiveness comprised 0.22 QALYs per patient and year. Best practice was cost-effective for more than 90% of all iterations (ICER for the baseline scenario: €2,109.25/QALY). Sensitivity analysis demonstrated that the findings remain robust. Considering the stroke incidence in Greece, the annual additional cost to implement best practice was calculated to be between 0.07%-0.15% of the total health expenditure.Best practice stroke treatment was cost-effective and affordable in a case study based on Greece. The results could be leveraged by including effects of preventive policies and rehabilitation. They also highlight the importance of adopting modern treatment strategies from a cost-effectiveness perspective, apart from the improved clinical outcomes.

Diagnostic radiological examinations as well as interventional radiological therapies are performed at a steadily increasing rate amidst increasingly limited resources in healthcare systems. Given their potential to contribute decisively to optimized therapy, in most cases associated short-term direct costs can be well justified from a clinical perspective. However, to realize their clinical benefits, they must also succeed in justifying them to payers and policymakers. Therefore, the aim of this work is to present suitable methods for economic analysis of radiological precedures and to elaborate their relevance for radiology.Methods and metrics of cost-effectiveness analysis are presented and then exemplified using the example cases of MR mammography and interventional treatment of oligometastatic tumor disease of the liver.Cost-effectiveness considerations, taking into account long-term gains in lifespan and quality of life, as well as potential savings through improved treatment planning, do often objectively and credibly justify short-term additional costs.Cost-effectiveness analyses performed with radiological and health economic expertise can support the establishment of new radiological technologies in diagnostics and therapy.· When radiological procedures are employed, short-term costs are often offset by significant long-term benefits.. · Radiological examinations and therapies must be justified in the context of limited economic resources.. · Economic methodologies can be used to quantify the quality and cost-effectiveness of radiological methods.. · Such analyses as well as targeted training should be encouraged to provide greater transparency..· Froelich MF, Kunz WG, Tollens F et al. Cost-effectiveness analysis in radiology: methods, results and implications. Fortschr Röntgenstr 2022; 194: 29 - 38. Diagnostische radiologische Untersuchungen sowie interventionell-radiologische Therapien werden mit stetiger Steigerungsrate im Spannungsfeld zunehmend begrenzter Ressourcen in Gesundheitssystemen durchgeführt. Vor dem Hintergrund ihres Potenzials, zu einer optimierten Therapie entscheidend beizutragen, lassen sich mit ihnen assoziierte kurzfristige, direkte Kosten in den meisten Fällen aus klinischer Sicht gut rechtfertigen. Um ihre klinischen Vorteile jedoch realisieren zu können, muss zusätzlich ihre Rechtfertigung gegenüber Kostenträgern und politischen Entscheidungsträgern gelingen. Ziel dieser Arbeit ist daher, geeignete Methoden zur ökonomischen Analyse radiologischer Maßnahmen darzustellen und ihre Relevanz für die Radiologie zu erarbeiten. Es werden Methoden und Messgrößen der Kosteneffektivitätsanalyse zunächst vorgestellt und dann an den Beispielfällen der MR-Mammografie sowie der interventionellen Behandlung einer oligometastatischen Tumorerkrankung der Leber beispielhaft demonstriert. Die Kosteneffektivitätsbetrachtung unter Berücksichtigung langfristiger Gewinne an Lebenszeit und -qualität sowie möglicher Einsparpotenziale mittels einer verbesserten Therapieplanung ist oft in der Lage, kurzfristige Zusatzkosten objektiv und glaubwürdig zu rechtfertigen. Mit radiologischer und gesundheitsökonomischer Expertise durchgeführte Kosteneffektivitätsanalysen können der Rechtfertigung und Etablierung neuer radiologischer Technologien in Diagnostik und Therapie dienen. · In der Radiologie stehen kurzfristige Kosten häufig einem deutlichen langfristigen Nutzen gegenüber.. · Radiologische Untersuchungen und Therapien müssen im Kontext begrenzter ökonomischer Ressourcen gerechtfertigt werden.. · Mittels ökonomischer Methoden lassen sich die Qualität und Kosteneffektivität radiologischer Methoden quantifizieren.. · Zur besseren Sichtbarkeit sollten derartige Analysen und zielgerichtete Weiterbildungen gefördert werden..· Froelich MF, Kunz WG, Tollens F et al. Cost-effectiveness analysis in radiology: methods, results and implications. Fortschr Röntgenstr 2022; 194: 29 – 38.

Background: Neurologic symptom severity and deterioration at 24 hours (h) predict long-term outcomes in patients with acute large vessel occlusion (LVO) stroke of the anterior circulation. We aimed to examine the association of baseline multiparametric CT imaging and clinical factors with the course of neurologic symptom severity in the first 24 h after endovascular treatment (EVT). Methods: Patients with LVO stroke of the anterior circulation were selected from a prospectively acquired consecutive cohort of patients who underwent multiparametric CT, including non-contrast CT, CT angiography and CT perfusion before EVT. The symptom severity was assessed on admission and after 24 h using the 42-point National Institutes of Health Stroke Scale (NIHSS). Clinical and imaging data were compared between patients with and without early neurological deterioration (END). END was defined as an increase in ≥4 points, and a significant clinical improvement as a decrease in ≥4 points, compared to NIHSS on admission. Multivariate regression analyses were used to determine independent associations of imaging and clinical parameters with NIHSS score increase or decrease in the first 24 h. Results: A total of 211 patients were included, of whom 38 (18.0%) had an END. END was significantly associated with occlusion of the internal carotid artery (odds ratio (OR), 4.25; 95% CI, 1.90–9.47) and the carotid T (OR, 6.34; 95% CI, 2.56–15.71), clot burden score (OR, 0.79; 95% CI, 0.68–0.92) and total ischemic volume (OR, 1.01; 95% CI, 1.00–1.01). In a comprehensive multivariate analysis model including periprocedural parameters and complications after EVT, carotid T occlusion remained independently associated with END, next to reperfusion status and intracranial hemorrhage. Favorable reperfusion status and small ischemic core volume were associated with clinical improvement after 24 h. Conclusions: The use of imaging parameters as a surrogate for early NIHSS progression in an acute LVO stroke after EVT reached limited performance with only carotid T occlusion as an independent predictor of END. Reperfusion status and early complications in terms of intracranial hemorrhage are critical factors that influence patient outcome in the acute stroke phase after EVT.

BackgroundThe added value of intravenous (IV) alteplase in large vessel occlusion (LVO) stroke over and beyond endovascular treatment (EVT) is controversial. We compared the long-term costs and cost-effectiveness of a direct-to-EVT paradigm in LVO stroke patients presenting directly to the mothership hospital to concurrent EVT and IV alteplase.MethodsWe used a decision model consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes. Outcome data were from the DIRECT-MT trial (NCT03469206). Incremental cost-effectiveness ratios and net monetary benefits were calculated and probabilistic sensitivity analysis was performed. Analysis was performed from a healthcare perspective and a societal perspective using both a minimal assumed alteplase cost of US$1 and true alteplase cost.ResultsWhen assuming a minimal cost of alteplase of $1, EVT with concurrent IV alteplase resulted in incremental lifetime cost of $5664 (healthcare perspective)/$4804 (societal perspective) and a decrement of 0.25 quality-adjusted life years (QALYs) compared with EVT only, indicating dominance of the EVT only approach. Net monetary benefits were consistently higher for EVT only compared with EVT with concurrent alteplase. Probabilistic sensitivity analysis showed increased costs without an increase in QALYs for EVT and concurrent IV alteplase compared with EVT only. Results were even more in favor of EVT when the true cost of alteplase was used for analysis.ConclusionEVT without concurrent alteplase is the preferred strategy from a health economic standpoint.

Abstract Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. Key Points • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

Simple Summary Colorectal cancer is among the most prevalent cancers worldwide, with every second patient developing liver metastasis during their illness. For treatment of oligometastatic patients, there are several alternatives such as surgery, microwave ablation (MWA) and radiofrequency ablation (RFA). Our aim was to evaluate the cost-effectiveness for each strategy, accounting for short- and long-term costs and efficacy. The analysis demonstrated that MWA and surgery offer a comparable efficacy. MWA was the most cost-effective strategy in intermediate resource settings, and can be considered a cost-effective alternative to surgery in high resource settings. Abstract Background: Colorectal cancer is among the most prevalent cancer entities worldwide, with every second patient developing liver metastases during their illness. For local treatment of liver metastases, a surgical approach as well as ablative treatment options, such as microwave ablation (MWA) and radiofrequency ablation (RFA), are available. The aim of this study is to evaluate the cost-effectiveness of RFA, MWA and surgery in the treatment of liver metastases of oligometastatic colorectal cancer (omCRC) that are amenable for all investigated treatment modalities. Methods: A decision analysis based on a Markov model assessed lifetime costs and quality-adjusted life years (QALY) related to the treatment strategies RFA, MWA and surgical resection. Input parameters were based on the best available and most recent evidence. Probabilistic sensitivity analyses (PSA) were performed with Monte Carlo simulations to evaluate model robustness. The percentage of cost-effective iterations was determined for different willingness-to-pay (WTP) thresholds. Results: The base-case analysis showed that surgery led to higher long-term costs compared to RFA and MWA (USD 41,848 vs. USD 36,937 vs. USD 35,234), while providing better long-term outcomes than RFA, yet slightly lower than MWA (6.80 vs. 6.30 vs. 6.95 QALYs for surgery, RFA and MWA, respectively). In PSA, MWA was the most cost-effective strategy for all WTP thresholds below USD 80,000 per QALY. Conclusions: In omCRC patients with liver metastases, MWA and surgery are estimated to provide comparable efficacy. MWA was identified as the most cost-effective strategy in intermediate resource settings and should be considered as an alternative to surgery in high resource settings.

Background and ObjectivesTo test the hypothesis that CT hypoperfusion-hypodensity mismatch identifies patients with ischemic stroke within 4.5 hours of symptom onset.MethodsWe therefore performed the Retrospective Multicenter Hypoperfusion-Hypodensity Mismatch for The identification of Patients With Stroke Within 4.5 Hours study of patients with acute ischemic stroke and known time of symptom onset. The predictive values of hypoperfusion-hypodensity mismatch for the identification of patients with symptom onset within 4.5 hours were the main outcome measure.ResultsOf 666 patients, 548 (82.3%) had multimodal CT within 4.5 hours and 118 (17.7%) beyond 4.5 hours. Hypoperfusion-hypodensity mismatch was visible in 516 (94.2%) patients with symptom onset within and in 30 (25.4%) patients beyond 4.5 hours. CT hypoperfusion-hypodensity mismatch identified patients within 4.5 hours of stroke onset with 94.2% (95% confidence interval [CI] 91.9%–95.8%) sensitivity, 74.6% (95% CI 66.0%–81.6%) specificity, 94.5% (95% CI 92.3%–96.1%) positive predictive value, and 73.3% (95% CI 64.8%–80.4%) negative predictive value. Interobserver agreement for hypoperfusion-hypodensity mismatch was substantial (κ = 0.61, 95% CI 0.53–0.69).DiscussionPatients with acute ischemic stroke with absence of a hypodensity on native CT (NCCT) within the hypoperfused core lesion on perfusion CT (hypoperfusion-hypodensity mismatch) are likely to be within the time window of thrombolysis. Applying this method may guide the decision to use thrombolysis in patients with unknown time of stroke onset.Trial Registration InformationClinicalTrials.gov Identifier: NCT04277728.Classification of EvidenceThis study provides Class III evidence that CT hypoperfusion-hypodensity mismatch identifies patients with stroke within 4.5 hours of onset.

IntroductionExperimental stroke studies suggest an influence of the time of day of stroke onset on infarct progression. Whether this holds true after human stroke is unknown, but would have implications for the design of randomised controlled trials, especially those on neuroprotection.MethodsWe pooled data from 583 patients with anterior large-vessel occlusion stroke from three prospectively recruited cohorts. Ischaemic core and penumbra volumes were determined with CT perfusion using automated thresholds. Core growth was calculated as the ratio of core volume and onset-to-imaging time. To determine circadian rhythmicity, we applied multivariable linear and sinusoidal regression analysis adjusting for potential baseline confounders.ResultsPatients with symptom onset at night showed larger ischaemic core volumes on admission compared with patients with onset during the day (median, 40.2 mL vs 33.8 mL), also in adjusted analyses (p=0.008). Sinusoidal analysis indicated a peak of core volumes with onset at 11pm. Core growth was faster at night compared with day onset (adjusted p=0.01), especially for shorter onset-to-imaging times. In contrast, penumbra volumes did not change across the 24-hour cycle.DiscussionThese results suggest that human infarct progression varies across the 24-hour cycle with potential implications for the design and interpretation of neuroprotection trials.

Clinical neuroradiology 31(3), 799-810 (2021). doi:10.1007/s00062-021-01033-1, Published by Urban & Vogel, München

BackgroundThe effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population.MethodsA Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of €80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs.ResultsEVT administered 1 min faster resulted in a median NMB of €309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -€15, IQR: −65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs.ConclusionOne-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs.

Objective The mutation of the ‘telomerase reverse transcriptase gene promoter’ (TERTp) has been identified as an important factor for individual prognostication and tumorigenesis and will be implemented in upcoming glioma classifications. Uptake characteristics on dynamic 18F-FET PET have been shown to serve as additional imaging biomarker for prognosis. However, data on the correlation of TERTp-mutational status and amino acid uptake on dynamic 18F-FET PET are missing. Therefore, we aimed to analyze whether static and dynamic 18F-FET PET parameters are associated with the TERTp-mutational status in de-novo IDH-wildtype glioblastoma and whether a TERTp-mutation can be predicted by dynamic 18F-FET PET. Methods Patients with de-novo IDH-wildtype glioblastoma, WHO grade IV, available TERTp-mutational status and dynamic 18F-FET PET scan prior to any therapy were included. Here, established clinical parameters maximal and mean tumor-to-background-ratios (TBRmax/TBRmean), the biological-tumor-volume (BTV) and minimal-time-to-peak (TTPmin) on dynamic PET were analyzed and correlated with the TERTp-mutational status. Results One hundred IDH-wildtype glioblastoma patients were evaluated; 85/100 of the analyzed tumors showed a TERTp-mutation (C228T or C250T), 15/100 were classified as TERTp-wildtype. None of the static PET parameters was associated with the TERTp-mutational status (median TBRmax 3.41 vs. 3.32 (p=0.362), TBRmean 2.09 vs. 2.02 (p=0.349) and BTV 26.1 vs. 22.4 ml (p=0.377)). Also, the dynamic PET parameter TTPmin did not differ in both groups (12.5 vs. 12.5 min, p=0.411). Within the TERTp-mutant subgroups (i.e., C228T (n=23) & C250T (n=62)), the median TBRmax (3.33 vs. 3.69, p=0.095), TBRmean (2.08 vs. 2.09, p=0.352), BTV (25.4 vs. 30.0 ml, p=0.130) and TTPmin (12.5 vs. 12.5 min, p=0.190) were comparable, too. Conclusion Uptake characteristics on dynamic 18F-FET PET are not associated with the TERTp-mutational status in glioblastoma However, as both, dynamic 18F-FET PET parameters as well as the TERTp-mutation status are well-known prognostic biomarkers, future studies should investigate the complementary and independent prognostic value of both factors in order to further stratify patients into risk groups.

A 16-year-old male patient underwent 18F-FDG PET/CT staging after multiple surgical resections and radiotherapy of an uncommon metastatic pediatric sebaceous carcinoma of the parotid gland. Initial PET/CT imaging exhibited a recurrent paravertebral metastasis (C4) as well as a metabolically active tumor tissue at the primary site. Follow-up PET/CT after radiotherapy of the cervical spine (C4) and four cycles of chemotherapy with cisplatin and palbociclib revealed complete functional remission in the cervical spine and partial remission at the primary site. This case illustrates the 18F-FDG-uptake behavior and the disease course of a very rare malignant epithelial tumor of the salivary glands.

Leptomeningeal collaterals play a pivotal role in acute ischemic stroke. While most collateral scores rely on subjective visual analysis, an objective quantification is possible using dynamic computed tomography (CT) angiography (dynCTA). The aim was to determine the value of collateral filling delay (CFD) as assessed by dynCTA for predicting subacute stroke complications.All subjects with isolated prebifurcation middle cerebral artery M1 occlusions were selected from an initial cohort of 2635 patients who underwent multiparametric CT for suspected stroke. The CFD was defined as the difference in time to peak enhancement between M2 segments of both hemispheres. Logistic regression analysis of CFD for space-occupying infarction (≥5 mm shift of brain tissue over the midline), parenchymal hematoma, and hemorrhagic transformation on follow-up imaging was performed.In this study 78 patients (47 female, median age 74 years) were included. The median CFD was 6.31 s (interquartile range [IQR] 4.00-8.64). The CFD values were correlated with qualitative collateral scores (p 0.05). Higher CFD was associated with the development of space-occupying infarction in univariable (odds ratio, OR = 1.28; p = 0.002) and multivariable regression analysis (OR = 1.48; p = 0.004). The CFD had no association with parenchymal hematoma or hemorrhagic transformation (p 0.05).A high CFD may serve as reproducible measure for collateralization and indicate development of increased risk of space-occupying infarction.

OBJECTIVES Interpretation of lung opacities in ICU supine chest radiographs remains challenging. We evaluated a prototype artificial intelligence algorithm to classify basal lung opacities according to underlying pathologies. DESIGN Retrospective study. The deep neural network was trained on two publicly available datasets including 297,541 images of 86,876 patients. PATIENTS One hundred sixty-six patients received both supine chest radiograph and CT scans (reference standard) within 90 minutes without any intervention in between. MEASUREMENTS AND MAIN RESULTS Algorithm accuracy was referenced to board-certified radiologists who evaluated supine chest radiographs according to side-separate reading scores for pneumonia and effusion (0 = absent, 1 = possible, and 2 = highly suspected). Radiologists were blinded to the supine chest radiograph findings during CT interpretation. Performances of radiologists and the artificial intelligence algorithm were quantified by receiver-operating characteristic curve analysis. Diagnostic metrics (sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) were calculated based on different receiver-operating characteristic operating points. Regarding pneumonia detection, radiologists achieved a maximum diagnostic accuracy of up to 0.87 (95% CI, 0.78-0.93) when considering only the supine chest radiograph reading score 2 as positive for pneumonia. Radiologist's maximum sensitivity up to 0.87 (95% CI, 0.76-0.94) was achieved by additionally rating the supine chest radiograph reading score 1 as positive for pneumonia and taking previous examinations into account. Radiologic assessment essentially achieved nonsignificantly higher results compared with the artificial intelligence algorithm: artificial intelligence-area under the receiver-operating characteristic curve of 0.737 (0.659-0.815) versus radiologist's area under the receiver-operating characteristic curve of 0.779 (0.723-0.836), diagnostic metrics of receiver-operating characteristic operating points did not significantly differ. Regarding the detection of pleural effusions, there was no significant performance difference between radiologist's and artificial intelligence algorithm: artificial intelligence-area under the receiver-operating characteristic curve of 0.740 (0.662-0.817) versus radiologist's area under the receiver-operating characteristic curve of 0.698 (0.646-0.749) with similar diagnostic metrics for receiver-operating characteristic operating points. CONCLUSIONS Considering the minor level of performance differences between the algorithm and radiologists, we regard artificial intelligence as a promising clinical decision support tool for supine chest radiograph examinations in the clinical routine with high potential to reduce the number of missed findings in an artificial intelligence-assisted reading setting.

Radiotherapy and radiation oncology play a key role in the clinical management of patients suffering from oncological diseases. In clinical routine, anatomic imaging such as contrast-enhanced CT and MRI are widely available and are usually used to improve the target volume delineation for subsequent radiotherapy. Moreover, these modalities are also used for treatment monitoring after radiotherapy. However, some diagnostic questions cannot be sufficiently addressed by the mere use standard morphological imaging. Therefore, positron emission tomography (PET) imaging gains increasing clinical significance in the management of oncological patients undergoing radiotherapy, as PET allows the visualization and quantification of tumoral features on a molecular level beyond the mere morphological extent shown by conventional imaging, such as tumor metabolism or receptor expression. The tumor metabolism or receptor expression information derived from PET can be used as tool for visualization of tumor extent, for assessing response during and after therapy, for prediction of patterns of failure and for definition of the volume in need of dose-escalation. This review focuses on recent and current advances of PET imaging within the field of clinical radiotherapy / radiation oncology in several oncological entities (neuro-oncology, head & neck cancer, lung cancer, gastrointestinal tumors and prostate cancer) with particular emphasis on radiotherapy planning, response assessment after radiotherapy and prognostication.

To assess the diagnostic utility of different perfusion algorithms for the detection of angiographical terial spasm.During a 2-year period, 45 datasets from 29 patients (54.2±10,75y, 20F) with suspected cerebral vasospasm after aneurysmal subarachnoid hemorrhage were included. Volume Perfusion CT (VPCT), Non-enhanced CT (NCT) and angiography were performed within 6hours post-ictus. Perfusion maps were generated using a maximum slope (MS) and a deconvolution-based approach (DC). Two blinded neuroradiologists independently evaluated MS and DC maps regarding vasospasm-related perfusion impairment on a 3-point Likert-scale (0=no impairment, 1=impairment affecting50%, 2=impairment affecting50% of vascular territory). A third independent neuroradiologist assessed angiography for presence and severity of arterial narrowing on a 3-point Likert scale (0=no narrowing, 1=narrowing affecting50%, 2=narrowing affecting50% of artery diameter). MS and DC perfusion maps were evaluated regarding diagnostic accuracy for angiographical arterial spasm with angiography as reference standard. Correlation analysis of angiography findings with both MS and DC perfusion maps was additionally performed. Furthermor, the agreement between MS and DC and inter-reader agreement was assessed.DC maps yielded significantly higher diagnostic accuracy than MS perfusion maps (DC:AUC=.870; MS:AUC=.805; P=0.007) with higher sensitivity for DC compared to MS (DC:sensitivity=.758; MS:sensitivity=.625). DC maps revealed stronger correlation with angiography than MS (DC: R=.788; MS: R=694;=0.001). MS and DC showed substantial agreement (Kappa=.626). Regarding inter-reader analysis, (almost) perfect inter-reader agreement was observed for both MS and DC maps (Kappa≥981).DC yields significantly higher diagnostic accuracy for the detection of angiographic arterial spasm and higher correlation with angiographic findings compared to MS.

To assess the prognostic value of pre-therapeutic computed tomography (CT) attenuation of liver metastases for overall survival (OS) in metastatic colorectal cancer (mCRC). In the open-label, randomised, prospective phase-III FIRE-3 trial, patients with histologically confirmed mCRC received fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) with either cetuximab or bevacizumab. Participating patients gave written informed consent prior to study entry. In CT at baseline (portal venous phase, slice thickness ≤5 mm), mean attenuation [Hounsfield units (HU)] of liver metastases was retrospectively assessed by semi-automated volumetry. Its prognostic influence on OS was analysed in Kaplan-Meier-analysis and Cox proportional hazard regression and an optimal threshold was determined. In FIRE-3, 592 patients were enrolled between 2007 and 2012. Among the 347 patients eligible for liver volumetry, median baseline CT attenuation of liver metastases was 59.67 HU [interquartile range (IQR), 49.13, 68.85]. Increased attenuation was associated with longer OS {per 10 HU: hazard ratio (HR), 0.85 [95% confidence interval (CI), 0.78, 0.93], p < 0.001}. The optimised threshold (≥61.62 HU) was a strong predictor for increased OS [median, 21.3 vs 30.6 months; HR, 0.61 (95% CI, 0.47, 0.80), p < 0.001]. Multivariate regression controlling for correlated and further prognostic factors confirmed this [HR, 0.60 (95% CI, 0.45, 0.81), p = 0.001]. Furthermore, mean attenuation ≥61.62 HU was significantly associated with increased early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012). Increased mean baseline CT attenuation of liver metastases may identify mCRC patients with prolonged OS and better tumour response. • In colorectal cancer, increased attenuation of liver metastases in baseline computed tomography is a prognostic factor for prolonged OS (p < 0.001). • A threshold of ≥61.62 HU was determined as optimal cut-off to identify patients with prolonged OS (p < 0.001), early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012).

We aimed to determine the diagnostic yield and accuracy of coronary CT angiography (CCTA) in patients referred for invasive coronary angiography (ICA) based on clinical concern for coronary artery disease (CAD) and an abnormal nuclear stress myocardial perfusion imaging (MPI) study. We enrolled 100 patients (84 male, mean age 59.6 ± 8.9 years) with an abnormal MPI study and subsequent referral for ICA. Each patient underwent CCTA prior to ICA. We analyzed the prevalence of potentially obstructive CAD (≥50% stenosis) on CCTA and calculated the diagnostic accuracy of ≥50% stenosis on CCTA for the detection of clinically significant CAD on ICA (defined as any ≥70% stenosis or ≥50% left main stenosis). On CCTA, 54 patients had at least one ≥50% stenosis. With ICA, 45 patients demonstrated clinically significant CAD. A positive CCTA had 100% sensitivity and 84% specificity with a 100% negative predictive value and 83% positive predictive value for clinically significant CAD on a per patient basis in MPI positive symptomatic patients. In conclusion, almost half (48%) of patients with suspected CAD and an abnormal MPI study demonstrate no obstructive CAD on CCTA.

ObjectiveAmong ischemic stroke patients with negative CT angiography (CTA), we aimed to determine the predictive value of enhanced distal vessel occlusion detection using CT perfusion postprocessing (waveletCTA) for the treatment effect of IV thrombolysis (IVT).MethodsPatients were selected from 1,851 consecutive patients who had undergone CT perfusion. Inclusion criteria were (1) significant cerebral blood flow (CBF) deficit, (2) no occlusion on CTA, and (3) infarction confirmed on follow-up. Favorable morphologic response was defined as smaller values of final infarction volume divided by initial CBF deficit volume (FIV/CBF). Favorable functional outcome was defined as modified Rankin Scale score of ≤2 after 90 days and decrease in NIH Stroke Scale score of ≥3 from admission to 24 hours (∆NIHSS).ResultsAmong patients with negative CTA (n = 107), 58 (54%) showed a distal occlusion on waveletCTA. There was no difference between patients receiving IVT (n = 57) vs supportive care (n = 50) regarding symptom onset, early ischemic changes, perfusion mismatch, or admission NIHSS score (all p > 0.05). In IVT-treated patients, the presence of an occlusion was an independent predictor of a favorable morphologic response (FIV/CBF: β −1.43; 95% confidence interval [CI] −1.96, −0.83; p = 0.001) and functional outcome (90-day modified Rankin Scale: odds ratio 7.68; 95% CI 4.33–11.51; p = 0.039; ∆NIHSS: odds ratio 5.76; 95% CI 3.98–8.27; p = 0.013), while it did not predict outcome in patients receiving supportive care (all p > 0.05).ConclusionIn stroke patients with negative CTA, distal vessel occlusions as detected by waveletCTA are an independent predictor of a favorable response to IVT.

Background and Purpose— Ipsilateral thalamic diaschisis (ITD) describes the reduction of thalamic function, metabolism, and perfusion resulting from a distant lesion of the ipsilateral hemisphere. Our aim was to evaluate the perfusion characteristics and clinical impact of ITD in acute middle cerebral artery stroke, which does not directly affect the thalamus. Methods— One hundred twenty-four patients with middle cerebral artery infarction were selected from a prospectively acquired cohort of 1644 patients who underwent multiparametric computed tomography (CT), including CT perfusion for suspected stroke. Two blinded readers evaluated the occurrence of ITD, defined as ipsilateral thalamic hypoperfusion present on ≥2 CT perfusion maps. Perfusion alterations were defined according to the Alberta Stroke Program Early CT Score regions. Final infarction volume and subacute complications were assessed on follow-up imaging. Clinical outcome was quantified using the modified Rankin Scale. Multivariable linear and ordinal logistic regression analysis were applied to identify independent associations. Results— ITD was present in 25/124 subjects (20.2%, ITD+). In ITD+ subjects, perfusion of the caudate nucleus, internal capsule, and lentiform nucleus was more frequently affected than in ITD− patients (each with P P =0.002) and cerebral blood volume ( P P =0.021) were observed. There was no independent association of ITD with final infarction volume or clinical outcome at discharge in treatment subgroups (each with P >0.05). ITD had no influence on the development of subacute stroke complications. Conclusions— ITD in the form of thalamic hypoperfusion is a frequent CT perfusion finding in the acute phase in middle cerebral artery stroke patients with marked involvement of subcortical areas. ITD does not result in thalamic infarction and had no independent impact on patient outcome. Notably, ITD was misclassified as part of the ischemic core by automated software, which might affect patient selection in CT perfusion–based trials.

Rationale and Objectives To determine the intraindividual impact of radiation dose reduction in abdominal computed tomography (CT) on diagnostic performance in patients with suspected appendicitis. Materials and Methods This study was approved by the institutional review board. Seventy-five patients who underwent standard contrast-enhanced abdominal CT for suspected appendicitis between 2004 and 2009 were retrospectively included. Low-dose CT reconstructions with 75%, 50%, and 25% of the original radiation dose level were generated by applying realistic reduced-dose simulation. Two blinded, independent readers assessed image quality, signal-to-noise ratio, and diagnostic confidence on each dataset. Diagnostic accuracy for detection of appendicitis and complications were calculated for each reader. Paired univariate tests were used to determine intraindividual differences. Results Among 75 subjects included in the analysis (57% female, mean age: 41 ± 18 years), the prevalence of histopathologically confirmed appendicitis was 59%. Signal-to-noise ratio and subjective image quality of 50% and 25% reduced-dose CTs were significantly lower than the reference datasets (all P Conclusions Our results indicate that diagnostic accuracy in abdominal CT acquisitions acquired at 75% and 50% of radiation dose is maintained in patients with suspected appendicitis, whereas further reduction of radiation exposition is associated with decreased diagnostic performance.

Existing quantitative imaging biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials. • Data-driven processes like radiomics risk false discoveries due to high-dimensionality of the dataset compared to sample size, making adequate diversity of the data, cross-validation and external validation essential to mitigate the risks of spurious associations and overfitting. • Use of radiomic signatures within clinical trials requires multistep standardisation of image acquisition, image analysis and data mining processes. • Biological correlation may be established after clinical validation but is not mandatory.

Purpose To determine the impact of patient age on the cost-effectiveness of endovascular therapy (EVT) in addition to standard care (SC) in large-vessel-occlusion stroke for patients aged 50 to 100 years in the United States. Materials and Methods A decision-analytic Markov model was used to estimate direct and indirect lifetime costs and quality-adjusted life years (QALYs). Age-dependent input parameters were obtained from the literature. Deterministic and probabilistic sensitivity analysis for age at index stroke were used. The willingness-to-pay (WTP) was set to thresholds of $50 000, $100 000, and $150 000 per QALY. The study applied a U.S. setting for health care and societal perspectives. Incremental costs and effectiveness were derived from deterministic and probabilistic sensitivity analysis. Acceptability rates at different WTP thresholds were determined. Results EVT+SC was the dominant strategy in patients aged 50 to 79 years. The highest incremental effectiveness (2.61 QALYs) and cost-savings (health care perspective, $99 555; societal perspective, $146 385) were obtained in 50-year-old patients. In octogenarians (80-89 years), EVT+SC led to incremental QALYs at incremental costs with acceptability rates of more than 85%, more than 99%, and more than 99% at a WTP of $50 000, $100 000, and $150 000 per QALY, respectively. In nonagenarians (90-99 years), acceptability rates at a WTP of $50 000 per QALY dropped but stayed higher than 85% and higher than 95% at thresholds of $100 000 and $150 000 per QALY. Conclusion Using contemporary willingness-to-pay thresholds in the United States, endovascular therapy in addition to standard care reduces lifetime costs for patients up to 79 years of age and is cost-effective for patients aged 80 to 100 years.

Intrahepatic cholangiocarcinoma is a highly aggressive malignancy with an increasing incidence in recent years. Prognosis is poor and most patients are not eligible for resection at the time of initial diagnosis due to the anatomic location, inadequate hepatic reserve, limiting comorbidities or metastatic disease. Several locoregional therapies from the field of interventional radiology exist for patients who are not amenable for surgery, or in case of local recurrence as a single treatment modality or combined with systemic treatment. To date, evidence is limited, with most conclusions drawn from single-center studies with small patient cohorts, often treated in the salvage situation or for local recurrence after initial resection. Nevertheless, the results are promising and suggest a survival benefit in selected patients. This narrative review focuses on the use of different locoregional treatment options for intrahepatic cholangiocarcinoma.

Introduction: The crosstalk of the gut microbiome and the human host can influence T-cell immune responses and has emerged as a modulator in cancer immunotherapy (Gopalakrishnan et al., 2018). Individual bacteria isolated from human fecal specimen were also shown to shape systemic and gut mucosal T cell repertoires (Geva-Zatorsky et al., 2017), and several commensal members of the human gut microbiome were recently associated with the kinetics of the reconstitution of peripheral immune cells after allo-HCT (Schluter et al., 2020). However, in patients treated with CAR T-cells a link between gut microbiome configurations and T-cell characteristics has not been described yet. Recently, we and others could associate low CAR T-cell expansion and dysfunction with treatment failure. Here, we hypothesize that certain gut microbes or even intestinal monodomination of facultative pathogens may correlate with CAR T-cell expansion and expression profile of immune checkpoint molecules which might impact treatment outcome. Methods: Patients with relapsed / refractory Diffuse-Large B-Cell Lymphoma (DLBCL) were treated with the CD19 specific CAR T-cell products Axicabtagene-Ciloleucel or Tisagenlecleucel at our institution from April 2019 to May 2021. Within this time-period, peripheral blood and fecal biospecimens from 23 patients were collected sequentially before, during and after CAR T-cell transfusion (specific time points: before lymphodepleting chemotherapy, day of CAR T-cell transfusion, day 7, day 14). CAR T-cells and the expression profile of immune checkpoint molecules (PD-1, TIM-3, LAG-3, 2B4) were studied by multiparameter flow cytometry. CAR T-cell peak expansion was assessed relatively (% CAR + T-cells of CD3+ T-cells) and absolutely (/ul). In addition, effector : target (E:T) ratios were estimated as absolute peak expansion of CAR T-cells (/ul) per tumor volume (as sum of the product of diameters based on Lugano criteria with up to 6 target lesions in cm 3). 16S rRNA gene sequencing was performed on 83 stool samples. Responder (R, complete or partial remission) were retrospectively assessed compared to Non-Responder (NR, stable or progressive disease) according to response assessment with PET-CT three months after CAR T-cell transfusion. Results: Higher alpha diversity (i.e., within-sample diversity) prior to CAR T-cell transfusion correlated positively with a favorable E:T ratio (CAR peak expansion/ul : tumor volume in cm 3, p=0.04, r=0.608; Fig. 1). Interestingly, the abundances of certain taxa prior to CAR T-cell transfusion correlated with the expansion of CAR T-cells in vivo. In particular we found a positive association with Pediococcus (p=0.018, r=0.751, FDR corrected) and with Anaerovoracaceae (E:T ratio, p=0.027, r=0.84, FDR corrected). Next, we studied the expression profile of immune checkpoint molecules on CAR T-cells in the context of microbial taxa in R vs NR patients. Notably, we observed a positive association between the frequency of CD8+ CAR T-cells devoid of inhibitory molecules (PD-1, TIM-3, LAG-3 and 2B4) and the relative abundance of the intestinal microbial genus Dorea (p=0.039, r=0.416: see Fig. 1). Furthermore, we found a higher relative abundance of Dorea (p=0.043) prior to transfusion in R compared to NR patients as well as significant positive associations of Dorea (p=0.0.008, r=0.54, not FDR corrected) and Pediococcus (p=0.047, r=0.462, not FDR corrected) with progression free survival . Conclusion: For the first time, we describe associations between the compositional changes of the gut microbiome and kinetics as well as immune characteristics of CAR T-cell therapy in patients with relapsed / refractory DLBCL. In the future, our findings need to be validated in a larger patient cohort and might serve as a predictive biomarker for microbiome-based patient assessment and microbiome-targeted therapeutic approaches to identify benefiting patients and to improve outcome. Figure 1 Figure 1. Disclosures Blumenberg: Kite/Gilead: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; BMS/Celgene: Research Funding; Janssen: Research Funding. von Bergwelt: MSD Sharpe & Dohme: Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding, Speakers Bureau; Kite/Gilead: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria, Research Funding, Speakers Bureau; Mologen: Honoraria, Research Funding, Speakers Bureau; Miltenyi: Honoraria, Research Funding, Speakers Bureau. Buecklein: Amgen: Consultancy, Honoraria; BMS / Celgene: Consultancy, Research Funding; Kite / Gilead: Consultancy, Honoraria, Other: Congress and travel support , Research Funding; Janssen: Consultancy; Miltenyi: Research Funding; Novartis: Consultancy, Other: Congress and travel support , Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau. Subklewe: Klinikum der Universität München: Current Employment; Takeda: Speakers Bureau; BMS/Celgene: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy, Research Funding, Speakers Bureau; MorphoSys: Research Funding; Novartis: Consultancy, Research Funding, Speakers Bureau; Roche: Research Funding; Seattle Genetics: Consultancy, Research Funding; Janssen: Consultancy; Pfizer: Consultancy, Speakers Bureau; Miltenyi: Research Funding; Amgen: Consultancy, Research Funding, Speakers Bureau.

Objective: The aim of this study was to test the diagnostic value of wavelet-based angiographic reconstruction of CT perfusion data (waveletCTA) to detect cerebral venous sinus thrombosis (CVST) in patients who underwent whole-brain CT perfusion imaging (WB-CTP). Materials and Methods: Datasets were retrospectively selected from an initial cohort of 2863 consecutive patients who had undergone multiparametric CT including WB-CTP. WaveletCTA was reconstructed from WB-CTP: the angiographic signal was generated by voxel-based wavelet transform of time attenuation curves (TACs) from WB-CTP raw data. In a preliminary clinical evaluation, waveletCTA was analyzed by 2 readers with respect to presence and location of CVST. Venous CT and MR angiography (venCTA/venMRA) served as reference standard. Diagnostic confidence for CVST detection and the quality of depiction for venous sections were evaluated on 5-point Likert scales. Thrombus extent was assessed by length measurements. The mean CT attenuation and waveletCTA signal of the thrombus and of flowing blood were quantified. Results: Sixteen patients were included: 10 patients with venCTA-/venMRAconfirmed CVST and 6 patients with arterial single-phase CT angiography (artCTA)-suspected but follow-up-excluded CVST. The reconstruction of waveletCTA was successful in all patients. Among the patients with confirmed CVST, waveletCTA correctly demonstrated presence, location, and extent of the thrombosis in 10/10 cases. In 6 patients with artCTA-suspected but follow-up-excluded CVST, waveletCTA correctly ruled out CVST in 5 patients. Reading waveletCTA in addition to artCTA significantly increased the diagnostic confidence concerning CVST compared with reading artCTA alone (4.4 vs 3.6, P = 0.044). The mean flowing blood-to-thrombus ratio was highest in waveletCTA, followed by venCTA and artCTA (146.2 vs 5.9 vs 2.6, each with P < 0.001). In waveletCTA, the venous sections were depicted better compared with artCTA (4.2 vs 2.6, P < 0.001), and equally well compared with venCTA/venMRA (4.2 vs 4.1, P = 0.374). Conclusions: WaveletCTA was technically feasible in CVST patients and reliably identified CVST in a preliminary clinical evaluation. WaveletCTA might serve as an additional reconstruction to rule out or incidentally detect CVST in patients who undergo WB-CTP.

68Ga-DOTATATE PET/CT enables detection of meningioma tissue based on somatostatin receptor 2 expression. Transosseous extension of intracranial meningiomas is known to be an important risk factor for tumor recurrence and patient mortality. We analyzed the diagnostic performance of 68Ga-DOTATATE PET/CT and contrast-enhanced MRI (CE-MRI) for the detection of osseous infiltration using qualitative and quantitative imaging parameters. Methods: In this institutional review board-approved retrospective study, subjects were selected from 327 consecutive 68Ga-DOTATATE PET/CT examinations for evaluation of confirmed or suspected meningioma. Inclusion criteria were CE-MRI within 30 d and pathology-confirmed meningioma diagnosis with inclusion or exclusion of transosseous extension as the standard of reference. Imaging was analyzed by two readers. Tracer uptake values and meningioma volumes were determined. χ2, Mann-Whitney U, Wilcoxon signed rank, and McNemar tests, as well as receiver-operating-characteristic analyses, were performed to compare variables and diagnostic performance. Results: Eighty-two patients fulfilled the inclusion criteria. Patients with transosseous extension of meningioma (n = 67) showed significantly larger lesions (median, 12.8 vs. 3.3 mL; P < 0.001) and significantly higher tracer uptake values (median SUVmax, 14.2 vs. 7.6; P = 0.011) than patients with extraosseous meningiomas (n = 15). 68Ga-DOTATATE PET/CT in comparison to CE-MRI performed at a higher sensitivity (98.5% vs. 53.7%) while maintaining high specificity (86.7% vs. 93.3%) in the detection of osseous involvement (P < 0.001). In receiver-operating-characteristic analysis, PET/CT assessment performed better than CE-MRI (area under the curve, 0.932 vs. 0.773). PET/CT- and CE-MRI-based volume estimation yielded comparable results for extraosseous meningiomas (P = 0.132) and the extraosseous part of transosseous meningiomas (P = 0.636), whereas the volume of the intraosseous part was assessed as significantly larger by PET/CT (P < 0.001). Conclusion:68Ga-DOTATATE PET/CT enables improved detection of the transosseous extension of intracranial meningiomas compared with CE-MRI.