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Abstract Rare cancers present significant challenges in diagnosis, treatment, and research, accounting for up to 25% of global cancer cases. Due to their rarity and atypical presentations, they are often misdiagnosed, resulting in late-stage detection and poor outcomes. Here, we describe a patient case with advanced metastatic nasopharynx NUT carcinoma, one of the rarest and most aggressive cancers. We conducted a comprehensive analysis of this patient’s tumor, including Tumor Mutation Burden, Microsatellite Instability, and genetic profiling to explore further putative druggable targets. The tumor exhibited high PD-L1 expression and showed a notable response to immune checkpoint inhibitors when combined with platinum-based radio-chemotherapy. Our findings indicate that checkpoint inhibitors could play a critical role in treating NUT carcinoma, offering new therapeutic avenues and hope for patients with this challenging diagnosis. Whether PD-L1 expression may be a useful predictor of immune checkpoint inhibitor efficacy warrants further research.

Abstract Background Metastatic prostate cancer remains a therapeutic challenge. Based on data of the STAMPEDE trial, patients with a low metastatic burden showed prolonged failure-free and overall survival when treated with prostate radio therapy (RT) in addition to standard of care (SOC). The objective of this study was to determine the cost-effectiveness of additional prostate RT compared to SOC alone for following subgroups: non-regional lymph node (NRLN) metastases, up to three bone metastases and four or more bone metastases. Methods A partitioned survival model was implemented with clinical data from STAMPEDE trial. Analyses were performed from a United States healthcare system perspective. Costs for treatment and adverse events were derived from Medicare coverage. Utilities for health states were derived from public databases and literature. Outcome measurements included incremental costs, effectiveness, and cost-effectiveness ratio. The willingness-to-pay threshold was set to USD 100,000 per quality-adjusted life year (QALY). Results Additional RT led to 0.92 incremental QALYs with increased costs of USD 26,098 with an incremental cost-effectiveness ratio (ICER) of USD 28,452/QALY for patients with only NRLN metastases and 3.83 incremental QALYs with increased costs of USD 153,490 with an ICER of USD 40,032/QALY for patients with up to three bone metastases. Sensitivity analysis showed robustness of the model regarding various parameters. In probabilistic sensitivity analysis using Monte Carlo simulation with 10,000 iterations, additional RT was found as the cost-effective strategy in over 96% for both subgroups iterations at a willingness-to-pay threshold of USD 100,000/QALYs. Conclusions Additional RT is cost-effective in patients with only NRLN metastases and up to three metastases compared to SOC.

Background: The prognosis of patients with advanced soft tissue sarcoma (STS) remains dismal. Trofosfamide (TRO) has been proposed as a well-tolerated oral maintenance therapy. This retrospective analysis aims to determine the value of this therapy. Methods: Fifty-nine patients with advanced STS who received TRO maintenance therapy between 2016 and 2022 were reviewed and analysed regarding clinical parameters and outcomes. Results: The median age was 48 years; the most common histological subtype was synovial sarcoma (n = 22, 37%), and 71% of patients (n = 42) presented with metastatic disease. No radiological evidence of disease (NED) before the start of maintenance was reported in 36% of patients (n = 21). The median follow-up was 38.2 months with a median maintenance duration of 9.0 months. The median event-free survival (EFS) and overall survival (OS) were 9.5 and 33.2 months, respectively. In metastatic patients achieving NED before the initiation of TRO, the median EFS was 29.4 months, while the median OS was not reached. In metastatic patients with anthracycline + ifosfamide (AI) as first-line induction therapy without prior metastasis-directed local therapy, the median EFS and OS from the start of AI were 13.9 and 26.8 months, respectively. Multivariate analysis of the overall cohort demonstrated that NED before the start of maintenance was significantly associated with a prolonged EFS (p = 0.024, hazard ratio [HR] = 0.26), and G2 histology correlated with longer OS (p = 0.030, HR = 0.16, reference: G3). Interpretation: Oral maintenance therapy with TRO appears to improve outcomes in patients with advanced STS. Metastatic patients who achieve NED through prior metastasectomy may particularly benefit from TRO maintenance.

Introduction This study evaluated the performance of magnetic resonance thermometry (MRT) during deep-regional hyperthermia (HT) in pelvic and lower-extremity soft-tissue sarcomas.Materials and methods 17 pelvic (45 treatments) and 16 lower-extremity (42 treatments) patients underwent standard regional HT and chemotherapy. Pairs of double-echo gradient-echo scans were acquired during the MR protocol 1.4 s apart. For each pair, precision was quantified using phase data from both echoes (‘dual-echo’) or only one (‘single-echo’) in- or excluding body fat pixels in the field drift correction region of interest. The precision of each method was compared to that of the MRT approach using a built-in clinical software tool (SigmaVision). Accuracy was assessed in three lower-extremity patients (six treatments) using interstitial temperature probes. The Jaccard coefficient quantified pretreatment motion; receiver operating characteristic analysis assessed its predictability for acceptable precision (

Abstract Purpose To assess the eligibility of patients with advanced or recurrent solid malignancies presented to a molecular tumor board (MTB) at a large precision oncology center for inclusion in trials with the endpoints objective response rate (ORR) or duration of response (DOR) based on Response Evaluation Criteria in Solid Tumors (RECIST version 1.1). Methods Prospective patients with available imaging at the time of presentation in the MTB were included. Imaging data was reviewed for objectifiable measurable disease (MD) according to RECIST v1.1. Additionally, we evaluated the patients with MD for representativeness of the identified measurable lesion(s) in relation to the overall tumor burden. Results 262 patients with different solid malignancies were included. 177 patients (68%) had MD and 85 (32%) had non-measurable disease (NMD) at the time point of MTB presentation in accordance with RECIST v1.1. MD was not representative of the overall tumor burden in eleven patients (6%). The main reasons for NMD were lesions with longest diameter shorter than 10 mm (22%) and non-measurable peritoneal carcinomatosis (18%). Colorectal cancer and malignant melanoma displayed the highest rates of MD (> 75%). In contrast, gastric cancer, head and neck malignancies, and ovarian carcinoma had the lowest rates of MD (

Abstract INTRODUCTION With the advent of disease‐modifying therapies, accurate assessment of biomarkers indicating the presence of disease‐associated amyloid beta (Aβ) pathology becomes crucial in patients with clinically suspected Alzheimer's disease (AD). We evaluated Aβ levels in cerebrospinal fluid (Aβ CSF) and Aβ levels in positron emission tomography (Aβ PET) biomarkers in a real‐world memory‐clinic setting to develop an efficient algorithm for clinical use. METHODS Patients were evaluated for AD‐related Aβ pathology from two independent cohorts (Ludwig Maximilian University [LMU], n = 402, and Medical University of Vienna [MUV], n = 144). Optimal thresholds of CSF biomarkers were deduced from receiver operating characteristic curves and validated against Aβ PET positivity. RESULTS In both cohorts, a CSF Aβ42/40 ratio ≥ 7.1% was associated with a low risk of a positive Aβ PET scan (negative predictive value: 94.3%). Implementing two cutoffs revealed 14% to 16% of patients with intermediate results (CSF Aβ42/40 ratio: 5.5%–7.1%), which had a strong benefit from Aβ PET imaging (44%–52% Aβ PET positivity). DISCUSSION A two‐cutoff approach for CSF Aβ42/40 including Aβ PET imaging at intermediate results provides an effective assessment of Aβ pathology in real‐world settings. Highlights We evaluated cerebrospinal fluid (CSF) and positron emission tomography (PET) amyloid beta (Aβ) biomarkers for Alzheimer's disease in real‐world cohorts. A CSF Aβ 42/40 ratio between 5.5% and 7.1% defines patients at borderline levels. Patients at borderline levels strongly benefit from additional Aβ PET imaging. Two‐cutoff CSF Aβ 42/40 and PET will allow effective treatment stratification.

Objective: In suspected acute ischemic stroke, it is now reasonable to expand the conventional “stroke protocol” (non-contrast computed tomography (NCCT), arterial CT angiography (CTA), and optionally CT perfusion (CTP)) to early and late venous head scans yielding a multiphase CTA (MP-CTA) to increase diagnostic confidence. Diagnostic reference levels (DRLs) have been defined for neither MP-CTA nor CTP. We therefore present dosimetry data, while also considering image quality, for a large, unselected patient cohort. Methods: A retrospective single-center study of 1790 patients undergoing the extended stroke protocol with three scanners (2× dual-source, DSCT; 1× single-source, SSCT) between 07/21 and 12/23 was conducted. For each sequence, we analyzed the radiation dose (volumetric CT dose index (CTDIvol); dose length product; effective dose); objective image quality using manually placed regions of interest (contrast-to-noise ratio (CNR)); and subjective image quality (4-point scale: 1 = non-diagnostic, 4 = excellent). The DRL was defined as the 75% percentile of the CTDIvol distribution. The Kruskal-Wallis test was used initially to test for overall equality of median values in each data group. Single post-test comparisons were performed with Dunn’s test, with an overall statistical significance level of 0.05. Results: Dosimetry values were significantly higher for SSCT (p < 0.001, each). Local DRLs ranged between 37.3 and 49.1 mGy for NCCT, 3.6–5.5 mGy for arterial CTA, 1.2–2.5 mGy each for early/late venous CTA, and 141.1–220.5 mGy for CTP. Protocol adjustment (DSCT-1: CTP) yielded a 28.2% dose reduction. The highest/lowest CNRs (arterial/early venous CTA, respectively) were recorded for SSCT/DSCT-2 (p < 0.001). Subjective image quality was rated excellent except for slightly increased MP-CTA noise at DSCT-2 (median = 3). Conclusions: Our data imply that additive MP-CTA scans only yield a minor increase in radiation exposure, particularly when using DSCT. CTP should be limited to selected patients.

Abstract Background Histopathology is the reference standard for diagnosing liver metastases of neuroendocrine tumors (NETs). Somatostatin receptor-positron emission tomography / computed tomography (SSR-PET/CT) has emerged as a promising non-invasive imaging modality for staging NETs. We aimed to assess the diagnostic accuracy of SSR-PET/CT in the identification of liver metastases in patients with proven NETs compared to histopathology. Methods Histopathologic reports of 139 resected or biopsied liver lesions of patients with known NET were correlated with matching SSR-PET/CTs and the positive/negative predictive value (PPV/NPV), sensitivity, specificity, and diagnostic accuracy of SSR-PET/CT were evaluated. PET/CT reading was performed by one expert reader blinded to histopathology and clinical data. Results 133 of 139 (95.7%) liver lesions showed malignant SSR-uptake in PET/CT while initial histopathology reported on ‘liver metastases of NET´ in 127 (91.4%) cases, giving a PPV of 91.0%. Re-biopsy of the initially histopathologically negative lesions (reference standard) nevertheless diagnosed ‘liver metastases of NET’ in 6 cases, improving the PPV of PET/CT to 95.5%. Reasons for initial false-negative histopathology were inadequate sampling in the sense of non-target biopsies. The 6 (4.3%) SSR-negative lesions were all G2 NETs with a Ki-67 between 2–15%. Conclusion SSR-PET/CT is a highly accurate imaging modality for the diagnosis of liver metastases in patients with proven NETs. However, we found that due to the well-known tumor heterogeneity of NETs, specifically in G2 NETs approximately 4–5% are SSR-negative and may require additional imaging with [18F]FDG PET/CT.

ObjectiveEndovascular thrombectomy (EVT) is the standard of care for acute large vessel occlusion stroke. Recently, the ANGEL-ASPECT and SELECT 2 trials showed improved outcomes in patients with acute ischemic Stroke presenting with large infarcts. The cost-effectiveness of EVT for this subpopulation of stroke patients has only been calculated using data from the previously published RESCUE-Japan LIMIT trial. It is, therefore, limited in its generalizability to an international population. With this study we primarily simulated patient-level costs to analyze the economic potential of EVT for patients with large ischemic stroke from a public health payer perspective based on the recently published data and secondarily identified determinants of cost-effectiveness.MethodsCosts and outcome of patients treated with EVT or only with the best medical care based on the recent prospective clinical trials ANGEL-ASPECT, SELECT2 and RESCUE-Japan LIMIT. A A Markov model was developed using treamtment outcomes derived from the most recent available literature. Deterministic and probabilistic sensitivity analyses addressed uncertainty.ResultsEndovascular treatment resulted in an incremental gain of 1.32 QALYs per procedure with cost savings of $17,318 per patient. Lifetime costs resulted to be most sensitive to the costs of the endovascular procedure.ConclusionEVT is a cost-saving (i.e., dominant) strategy for patients presenting with large ischemic cores defined by inclusion criteria of the recently published ANGEL-ASPECT, SELECT2, and RESCUE-Japan LIMIT trials in comparison to best medical care in our simulation. Prospective data of individual patients need to be collected to validate these results.

Abstract Background Pseudoprogression (PsPD) is a rare response pattern to immune checkpoint inhibitor (ICI) therapy in oncology. This study aims to reveal imaging features of PsPD, and their association to other relevant findings. Methods Patients with PsPD who had at least three consecutive cross-sectional imaging studies at our comprehensive cancer center were retrospectively analyzed. Treatment response was assessed according to immune Response Evaluation Criteria in Solid Tumors (iRECIST). PsPD was defined as the occurrence of immune unconfirmed progressive disease (iUPD) without follow-up confirmation. Target lesions (TL), non-target lesions (NTL), new lesions (NL) were analyzed over time. Tumor markers and immune-related adverse events (irAE) were correlated. Results Thirty-two patients were included (mean age: 66.7 ± 13.6 years, 21.9% female) with mean baseline STL of 69.7 mm ± 55.6 mm. PsPD was observed in twenty-six patients (81.3%) at FU1, and no cases occurred after FU4. Patients with iUPD exhibited the following: TL increase in twelve patients, (37.5%), NTL increase in seven patients (21.9%), NL appearance in six patients (18.8%), and combinations thereof in four patients (12.5%). The mean and maximum increase for first iUPD in sum of TL was 19.8 and 96.8 mm (+ 700.8%). The mean and maximum decrease in sum of TL between iUPD and consecutive follow-up was − 19.1 mm and − 114.8 mm (-60.9%) respectively. The mean and maximum sum of new TL at first iUPD timepoint were 7.6 and 82.0 mm respectively. In two patients (10.5%), tumor-specific serologic markers were elevated at first iUPD, while the rest were stable or decreased among the other PsPD cases (89.5%). In fourteen patients (43.8%), irAE were observed. Conclusions PsPD occurred most frequently at FU1 after initiation of ICI treatment. The two most prevalent reasons for PsPD were TL und NTL progression, with an increase in TL diameter commonly below + 100%. In few cases, PsPD was observed even if tumor markers were rising compared to baseline. Our findings also suggest a correlation between PsPD and irAE. These findings may guide decision-making of ICI continuation in suspected PsPD.

Abstract Background Chimeric antigen receptor T-cell therapy (CART) prolongs survival for patients with refractory or relapsed lymphoma. Discrepancies among different response criteria for lymphoma under CART were recently shown. Our objective was to evaluate reasons for discordance among different response criteria and their relation to overall survival. Methods Consecutive patients with baseline and follow-up imaging at 30 (FU1) and 90 days (FU2) after CART were included. Overall response was determined based on Lugano, Cheson, response evaluation criteria in lymphoma (RECIL) and lymphoma response to immunomodulatory therapy criteria (LYRIC). Overall response rate (ORR) and rates of progressive disease (PD) were determined. For each criterion reasons for PD were analyzed in detail. Results 41 patients were included. ORR was 68%, 68%, 63%, and 68% at FU2 by Lugano, Cheson, RECIL, and LYRIC, respectively. PD rates differed among criteria with 32% by Lugano, 27% by Cheson, 17% by RECIL, and 17% by LYRIC. Dominant reasons for PD according to Lugano were target lesion (TL) progression (84.6%), new appearing lesions (NL; 53.8%), non-TL progression (27.3%), and progressive metabolic disease (PMD; 15.4%). Deviations among the criteria for defining PD were largely explained by PMD of preexisting lesions that are defined as PD only by Lugano and non-TL progression, which is not defined as PD by RECIL and in some cases classified as indeterminate response by LYRIC. Conclusions Following CART, lymphoma response criteria show differences in imaging endpoints, especially in defining PD. The response criteria must be considered when interpreting imaging endpoints and outcomes from clinical trials.

Background and purposeAutomated perfusion imaging can detect stroke patients with unknown time of symptom onset who are eligible for thrombolysis. However, the availability of this technique is limited. We, therefore, established the novel concept of computed tomography (CT) hypoperfusion-hypodensity mismatch, i.e., an ischemic core lesion visible on cerebral perfusion CT without visible hypodensity in the corresponding native cerebral CT. We compared both methods regarding their accuracy in identifying patients suitable for thrombolysis.MethodsIn a retrospective analysis of the MissPerfeCT observational cohort study, patients were classified as suitable or not for thrombolysis based on established time window and imaging criteria. We calculated predictive values for hypoperfusion-hypodensity mismatch and automated perfusion imaging to compare accuracy in the identification of patients suitable for thrombolysis.ResultsOf 247 patients, 219 (88.7%) were eligible for thrombolysis and 28 (11.3%) were not eligible for thrombolysis. Of 197 patients who were within 4.5 h of symptom onset, 190 (96.4%) were identified by hypoperfusion-hypodensity mismatch and 88 (44.7%) by automated perfusion mismatch (p

Background Chimeric antigen receptor T-cell therapy (CART) is effective for patients with refractory or relapsed lymphoma with prolongation of survival. We aimed to improve the prediction of Lugano criteria for overall survival (OS) at 30-day follow-up (FU1) by including the pre-infusion tumor growth rate (TGRpre-BL) and its early change to 30-day FU1 imaging (TGRpost-BL).Methods Consecutive patients with pre-baseline (pre-BL), baseline (BL) and FU1 imaging with CT or positron emission tomography/CT before CART were included. TGR was defined as change of Lugano criteria-based tumor burden between pre-BL, BL and FU1 examinations in relation to days between imaging examinations. Overall response and progression-free survival were determined based on Lugano criteria. Proportional Cox regression analysis studied association of TGR with OS. For survival analysis, OS was analyzed using Kaplan-Meier survival curves.Results Fifty-nine out of 81 patients met the inclusion criteria. At 30-day FU1 8 patients (13.6%) had a complete response (CR), 25 patients (42.4%) a partial response (PR), 15 patients (25.4%) a stable disease (SD), and 11 patients (18.6%) a progressive disease (PD) according to CT-based Lugano criteria. The median TGRpre-BL was −0.6 mm2/day, 24.4 mm2/day, −5.1 mm2/day, and 18.6 mm2/day and the median TGRpost-BL was −16.7 mm2/day, −102.0 mm2/day, −19.8 mm2/day and 8.5 mm2/day in CR, PR, SD, and PD patients, respectively. PD patients could be subclassified into a cohort with an increase in TGR (7 of 11 patients (64%), PD TGRpre-to-post-BL INCR) and a cohort with a decrease in TGR (4 of 11 patients (36%), PD TGRpre-to-post-BL DECR) from pre-BL to post-BL. PD TGRpre-to-post-BL DECR patients exhibited similar OS to patients classified as SD, while PD TGRpre-to-post-BL INCR patients had significantly shorter OS (65 days vs 471 days, p

Abstract Background Lesion/tissue segmentation on digital medical images enables biomarker extraction, image-guided therapy delivery, treatment response measurement, and training/validation for developing artificial intelligence algorithms and workflows. To ensure data reproducibility, criteria for standardised segmentation are critical but currently unavailable. Methods A modified Delphi process initiated by the European Imaging Biomarker Alliance (EIBALL) of the European Society of Radiology (ESR) and the European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group was undertaken. Three multidisciplinary task forces addressed modality and image acquisition, segmentation methodology itself, and standards and logistics. Devised survey questions were fed via a facilitator to expert participants. The 58 respondents to Round 1 were invited to participate in Rounds 2–4. Subsequent rounds were informed by responses of previous rounds. Results/conclusions Items with ≥ 75% consensus are considered a recommendation. These include system performance certification, thresholds for image signal-to-noise, contrast-to-noise and tumour-to-background ratios, spatial resolution, and artefact levels. Direct, iterative, and machine or deep learning reconstruction methods, use of a mixture of CE marked and verified research tools were agreed and use of specified reference standards and validation processes considered essential. Operator training and refreshment were considered mandatory for clinical trials and clinical research. Items with a 60–74% agreement require reporting (site-specific accreditation for clinical research, minimal pixel number within lesion segmented, use of post-reconstruction algorithms, operator training refreshment for clinical practice). Items with ≤ 60% agreement are outside current recommendations for segmentation (frequency of system performance tests, use of only CE-marked tools, board certification of operators, frequency of operator refresher training). Recommendations by anatomical area are also specified.

Background and Purpose Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether a simple method of computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours. Methods This retrospective analysis of the MissPerfeCT study (August 2009 to November 2017) includes consecutive patients with known onset of symptoms from seven tertiary stroke centers. We developed a simplified algorithm based on region of interest (ROI) measurements to quantify water uptake of the ischemic lesion and thereby quantify time of symptom onset within and beyond 4.5 hours. Perfusion CT was used to identify ischemic brain tissue, and its density was measured in non-contrast CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. Results Of 263 patients, 204 (77.6%) had CT within 4.5 hours. Water uptake was significantly lower in patients with stroke onset within (6.7%; 95% confidence interval [CI], 6.0% to 7.4%) compared to beyond 4.5 hours (12.7%; 95% CI, 10.7% to 14.7%). The area under the curve for distinguishing these patient groups according to percentage water uptake was 0.744 with an optimal cut-off value of 9.5%. According to this cut-off the positive predictive value was 88.8%, sensitivity was 73.5%, specificity 67.8%, negative predictive value was 42.6%. Conclusions Ischemic stroke patients with unknown time of symptom onset can be identified as being within a timeframe of 4.5 hours using a ROI-based method to assess water uptake on admission non-contrast head CT.

Abstract Artificial intelligence (AI) algorithms evaluating [supine] chest radiographs ([S]CXRs) have remarkably increased in number recently. Since training and validation are often performed on subsets of the same overall dataset, external validation is mandatory to reproduce results and reveal potential training errors. We applied a multicohort benchmarking to the publicly accessible (S)CXR analyzing AI algorithm CheXNet, comprising three clinically relevant study cohorts which differ in patient positioning ([S]CXRs), the applied reference standards (CT-/[S]CXR-based) and the possibility to also compare algorithm classification with different medical experts’ reading performance. The study cohorts include [1] a cohort, characterized by 563 CXRs acquired in the emergency unit that were evaluated by 9 readers (radiologists and non-radiologists) in terms of 4 common pathologies, [2] a collection of 6,248 SCXRs annotated by radiologists in terms of pneumothorax presence, its size and presence of inserted thoracic tube material which allowed for subgroup and confounding bias analysis and [3] a cohort consisting of 166 patients with SCXRs that were evaluated by radiologists for underlying causes of basal lung opacities, all of those cases having been correlated to a timely acquired computed tomography scan (SCXR and CT within

ObjectiveEndovascular thrombectomy is a long-established therapy for acute basilar artery occlusion (aBAO). Unlike for anterior circulation stroke, cost-effectiveness of endovascular treatment has not been evaluated and is urgently needed to calculate expected health benefits and financial rewards. The aim of this study was therefore to simulate patient-level costs, analyze the economic potential of endovascular thrombectomy in patients with acute basilar artery occlusion (aBAO), and identify major determinants of cost-effectiveness.MethodsA Markov model was developed to compare outcome and cost parameters between patients treated by endovascular thrombectomy and patients treated by best medical care, based on four recent prospective clinical trials (ATTENTION, BAOCHE, BASICS, and BEST). Treatment outcomes were derived from the most recent literature. Uncertainty was addressed by deterministic and probabilistic sensitivity analyses. Willingness to pay per QALY thresholds were set at 1x gross domestic product per capita, as recommended by the World Health Organization.ResultsEndovascular treatment of acute aBAO stroke yielded an incremental gain of 1.71 quality-adjusted life-years per procedure with an incremental cost-effectiveness ratio of $7,596 per QALY. This was substantially lower than the Willingness to pay of $63,593 per QALY. Lifetime costs were most sensitive to costs of the endovascular procedure.ConclusionEndovascular treatment is cost-effective in patients with aBAO stroke.

Abstract Background Although endovascular therapy (EVT) improves clinical outcomes in patients with acute ischemic stroke, the time of EVT initiation significantly influences clinical outcomes and healthcare costs. This study evaluated the impact of EVT treatment delay on cost-effectiveness in China. Methods A model combining a short-term decision tree and long-term Markov health state transition matrix was constructed. For each time window of symptom onset to EVT, the probability of receiving EVT or non-EVT treatment was varied, thereby varying clinical outcomes and healthcare costs. Clinical outcomes and cost data were derived from clinical trials and literature. Incremental cost-effectiveness ratio and incremental net monetary benefits were simulated. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of the model. The willingness-to-pay threshold per quality-adjusted life-year (QALY) was set to ¥71,000 ($10,281). Results EVT performed between 61 and 120 min after the stroke onset was most cost-effective comparing to other time windows to perform EVT among AIS patients in China, with an ICER of ¥16,409/QALY ($2376) for performing EVT at 61–120 min versus the time window of 301–360 min. Each hour delay in EVT resulted in an average loss of 0.45 QALYs and 165.02 healthy days, with an average net monetary loss of ¥15,105 ($2187). Conclusions Earlier treatment of acute ischemic stroke patients with EVT in China increases lifetime QALYs and the economic value of care without any net increase in lifetime costs. Thus, healthcare policies should aim to improve efficiency of pre-hospital and in-hospital workflow processes to reduce the onset-to-puncture duration in China.

Background and Purpose The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. Methods In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient subgroup with unsuccessful recanalization was used to model the standard of care group. For modeling of lifetime estimates, pediatric and adult input parameters were obtained from the current literature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. Results The model results yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. Conclusions EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

ObjectivesLarge vessel occlusion (LVO) stroke patients routinely undergo interhospital transfer to endovascular thrombectomy capable centers. Imaging is often repeated with residual intravenous (IV) iodine contrast at post-transfer assessment. We determined imaging findings and the impact of residual contrast on secondary imaging. Anterior circulation LVO stroke patients were selected out of a consecutive cohort. Directly admitted patients were contrast naïve, and transferred patients had previously received IV iodine contrast for stroke assessment at the referring hospital. Two independent readers rated the visibility of residual contrast on non-contrast computed tomography (CT) after transfer and assessed the hyperdense vessel sign. Multivariate linear regression analysis was used to investigate the association of the Alberta Stroke Program Early CT score (ASPECTS) with prior contrast administration, time from symptom onset (TFSO), and CTP ischemic core volume in both directly admitted and transferred patients.ResultsWe included 161 patients, with 62 (39%) transferred and 99 (62%) directly admitted patients. Compared between these groups, transferred patients had a longer TFSO-to-imaging at our institution (median: 212 vs. 75 min, p < 0.001) and lower ASPECTS (median: 8 vs. 9, p < 0.001). Regression analysis presented an independent association of ASPECTS with prior contrast administration (β = −0.25, p = 0.004) but not with TFSO (β = −0.03, p = 0.65). Intergroup comparison between transferred and directly admitted patients pointed toward a stronger association between ASPECTS and CTP ischemic core volume in transferred patients (β = −0.39 vs. β = −0.58, p = 0.06). Detectability of the hyperdense vessel sign was substantially lower after transfer (66 vs. 10%, p < 0.001).ConclusionImaging alterations due to residual IV contrast are frequent in clinical practice and render the hyperdense vessel sign largely indetectable. Larger studies are needed to clarify the influence on the association between ASPECTS and ischemic core.

PurposeHigh tumor burden has emerged as a negative predictor of efficacy in chimeric antigen receptor T-cell therapy (CART) in patients with refractory or relapsed large B-cell lymphoma. This study analyzed the deviation among imaging-based tumor burden (TB) metrics and their association with progression-free (PFS) and overall survival (OS).Materials and methodsIn this single-center observational study, we included all consecutively treated patients receiving CD19 CART with available baseline PET-CT imaging. Imaging-based TB was determined based on response evaluation criteria in lymphoma (RECIL), the Lugano criteria, and metabolic tumor volume. Total, nodal and extranodal TB were represented, according to the respective criteria, by sum of longest diameters (TBRECIL), sum of product of perpendicular diameters (TBLugano), and metabolic tumor volume (TBMTV). Correlation statistics were used for comparison. Proportional Cox regression analysis studied the association of TB metrics with PFS and OS.Results34 consecutive patients were included (median age: 67 years, 41% female) with total median baseline TBRECIL of 12.5 cm, TBLugano of 4,030 mm2 and TBMTV of 330 mL. The correlation of TBRECIL and TBLugano with TBMTV was strong (ρ=0.744, p50% (HR=2.915, p=0.042), whereas total TBRECIL>50% and total TBLugano>50% were not significant (both p>0.05). None of the total TB metrics were associated with OS (all p>0.05).ConclusionPre-CART TB metrics vary significantly based on the assessment method, impacting their association with survival outcomes. The correlation between TBRECIL, TBLugano and TBMTV was influenced by disease phenotype and prior bridging therapy. TB method of assessment must be considered when interpreting the impact of TB on outcomes in clinical trials. Considering the heterogeneity, our results argue for standardization and harmonization across centers.

Testicular cancer is a rare disease; however, cure rates are high for all tumor stages. Mostly, the disease is diagnosed in an early (local) stage. We report the case of a 47-year-old male patient with a giant nonseminomatous germ cell tumor. At the time of diagnosis, the patient demonstrated a necrotizing and ulcerating growing mass in the left scrotum with an approximate size of 22 × 18 cm. According to the prognostic classification of the International Germ Cell Cancer Collaborative Group (IGCCCG 1997), the patient exhibited a high-risk profile due to alpha-fetoprotein >10,000 ng/mL and lactate dehydrogenase >10× the upper limit of normal in serum. Primary orchiectomy was infeasible due to the tumor’s size, the patient’s poor general condition and initial intensive care unit treatment. Primary systemic chemotherapy was applied. After 3 cycles of cisplatin, etoposide and bleomycin, along with 1 cycle of cisplatin, etoposide and ifosfamide, tumor resection with histomorphological examination showed a complete pathological response. Despite the delayed initiation of the therapy, primary chemotherapy was completed timely and showed promising results. Reasons for the late hospitalization were personal responsibilities regarding his family. Better awareness and knowledge of testicular cancer among young men might prevent the here reported delay of medical consultation and avoid testicular tumors of such enormous size. Psychosocial assessment and distress management is important as an integral part of comprehensive care of testicular cancer patients.

Abstract Background Characteristics of COVID-19 patients have mainly been reported within confirmed COVID-19 cohorts. By analyzing patients with respiratory infections in the emergency department during the first pandemic wave, we aim to assess differences in the characteristics of COVID-19 vs. Non-COVID-19 patients. This is particularly important regarding the second COVID-19 wave and the approaching influenza season. Methods We prospectively included 219 patients with suspected COVID-19 who received radiological imaging and RT-PCR for SARS-CoV-2. Demographic, clinical and laboratory parameters as well as RT-PCR results were used for subgroup analysis. Imaging data were reassessed using the following scoring system: 0 – not typical, 1 – possible, 2 – highly suspicious for COVID-19. Results COVID-19 was diagnosed in 72 (32,9%) patients. In three of them (4,2%) the initial RT-PCR was negative while initial CT scan revealed pneumonic findings. 111 (50,7%) patients, 61 of them (55,0%) COVID-19 positive, had evidence of pneumonia. Patients with COVID-19 pneumonia showed higher body temperature (37,7 ± 0,1 vs. 37,1 ± 0,1 °C; p = 0.0001) and LDH values (386,3 ± 27,1 vs. 310,4 ± 17,5 U/l; p = 0.012) as well as lower leukocytes (7,6 ± 0,5 vs. 10,1 ± 0,6G/l; p = 0.0003) than patients with other pneumonia. Among abnormal CT findings in COVID-19 patients, 57 (93,4%) were evaluated as highly suspicious or possible for COVID-19. In patients with negative RT-PCR and pneumonia, another third was evaluated as highly suspicious or possible for COVID-19 (14 out of 50; 28,0%). The sensitivity in the detection of patients requiring isolation was higher with initial chest CT than with initial RT-PCR (90,4% vs. 79,5%). Conclusions COVID-19 patients show typical clinical, laboratory and imaging parameters which enable a sensitive detection of patients who demand isolation measures due to COVID-19.

Abstract Background Prolonged myelosuppression following CD19-directed CAR T-cell transfusion represents an important, yet underreported, adverse event. The resulting neutropenia and multifactorial immunosuppression can facilitate severe infectious complications. Case presentation We describe the clinical course of a 59-year-old patient with relapsed/refractory DLBCL who received Axicabtagene-Ciloleucel (Axi-cel). The patient developed ASTCT grade I CRS and grade IV ICANS, necessitating admission to the neurological ICU and prolonged application of high-dose corticosteroids and other immunosuppressive agents. Importantly, neutropenia was profound (ANC

Abstract Recent immunotherapeutic approaches have evolved as powerful treatment options with high anti-tumour responses involving the patient’s own immune system. Passive immunotherapy applies agents that enhance existing anti-tumour responses, such as antibodies against immune checkpoints. Active immunotherapy uses agents that direct the immune system to attack tumour cells by targeting tumour antigens. Active cellular-based therapies are on the rise, most notably chimeric antigen receptor T cell therapy, which redirects patient-derived T cells against tumour antigens. Approved treatments are available for a variety of solid malignancies including melanoma, lung cancer and haematologic diseases. These novel immune-related therapeutic approaches can be accompanied by new patterns of response and progression and immune-related side-effects that challenge established imaging-based response assessment criteria, such as Response Evaluation Criteria in Solid tumours (RECIST) 1.1. Hence, new criteria have been developed. Beyond morphological information of computed tomography (CT) and magnetic resonance imaging, positron emission tomography (PET) emerges as a comprehensive imaging modality by assessing (patho-)physiological processes such as glucose metabolism, which enables more comprehensive response assessment in oncological patients. We review the current concepts of response assessment to immunotherapy with particular emphasis on hybrid imaging with 18F-FDG-PET/CT and aims at describing future trends of immunotherapy and additional aspects of molecular imaging within the field of immunotherapy.

Abstract 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.

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.

A 54-year-old patient presented with progressive pain for one month in the second finger of the right hand with an emphasis on the proximal interphalangeal (PIP) joint. Subsequent magnetic resonance imaging (MRI) showed a diffuse intraosseous lesion at the base of the middle phalanx with destruction of the cortical bone and extraosseous soft tissue. An expansively growing chondromatous bone tumor, e.g., a chondrosarcoma, was suspected. After incisional biopsy, the pathologic findings finally revealed, surprisingly, a metastasis of a poorly differentiated non-small cell adenocarcinoma of the lung. This case illustrates a rare but important differential diagnosis for painful finger lesions.

Response evaluation criteria in solid tumours (RECIST) v1.1 are currently the reference standard for evaluating efficacy of therapies in patients with solid tumours who are included in clinical trials, and they are widely used and accepted by regulatory agencies. This expert statement discusses the principles underlying RECIST, as well as their reproducibility and limitations. While the RECIST framework may not be perfect, the scientific bases for the anticancer drugs that have been approved using a RECIST-based surrogate endpoint remain valid. Importantly, changes in measurement have to meet thresholds defined by RECIST for response classification within thus partly circumventing the problems of measurement variability. The RECIST framework also applies to clinical patients in individual settings even though the relationship between tumour size changes and outcome from cohort studies is not necessarily translatable to individual cases. As reproducibility of RECIST measurements is impacted by reader experience, choice of target lesions and detection/interpretation of new lesions, it can result in patients changing response categories when measurements are near threshold values or if new lesions are missed or incorrectly interpreted. There are several situations where RECIST will fail to evaluate treatment-induced changes correctly; knowledge and understanding of these is crucial for correct interpretation. Also, some patterns of response/progression cannot be correctly documented by RECIST, particularly in relation to organ-site (e.g. bone without associated soft-tissue lesion) and treatment type (e.g. focal therapies). These require specialist reader experience and communication with oncologists to determine the actual impact of the therapy and best evaluation strategy. In such situations, alternative imaging markers for tumour response may be used but the sources of variability of individual imaging techniques need to be known and accounted for. Communication between imaging experts and oncologists regarding the level of confidence in a biomarker is essential for the correct interpretation of a biomarker and its application to clinical decision-making. Though measurement automation is desirable and potentially reduces the variability of results, associated technical difficulties must be overcome, and human adjudications may be required.

ObjectivesTo evaluate the cost-effectiveness of MR-mammography (MRM) vs. x-ray based mammography (XM) in two-yearly screening women of intermediate risk for breast cancer in the light of recent literature.MethodsDecision analysis and Markov modelling were used to compare cumulative costs (in US-$) and outcomes (in QALYs) of MRM vs. XM over the model runtime of 20 years. The perspective of the U.S. healthcare system was selected. Incremental cost-effectiveness ratios (ICER) were calculated and related to a willingness to pay-threshold of $ 100,000 per QALY in order to evaluate the cost-effectiveness. Deterministic and probabilistic sensitivity analyses were conducted to test the impact of variations of the input parameters. In particular, variations of the rate of false positive findings beyond the first screening round and their impact on cost-effectiveness were assessed.ResultsBreast cancer screening with MRM resulted in increased costs and superior effectiveness. Cumulative average costs of $ 6,081 per woman and cumulative effects of 15.12 QALYs were determined for MRM, whereas screening with XM resulted in costs of $ 5,810 and 15.10 QALYs, resulting in an ICER of $ 13,493 per QALY gained. When the specificity of MRM in the second and subsequent screening rounds was varied from 92% to 99%, the ICER resulted in a range from $ 38,849 to $ 5,062 per QALY.ConclusionsBased on most recent data on the diagnostic performance beyond the first screening round, MRM may remain the economically preferable alternative in screening women of intermediate risk for breast cancer due to their dense breast tissue.

Rationale: Early evidence for the benefit of mechanical thrombectomy (MT) in pediatric patients with intracranial large vessel occlusion has been shown in previous retrospective cohorts. Higher-level evidence is needed to overcome the limitations of these studies such as the lack of a control group and the retrospective design. Randomized trials will very likely not be feasible, and several open questions remain, for example, the impact of arteriopathic etiologies or a possible lower age limit for MT. Save ChildS Pro therefore aims to demonstrate the safety and effectiveness of MT in pediatric patients compared to the best medical management and intravenous thrombolysis.Design: Save ChildS Pro is designed as a worldwide multicenter prospective registry comparing the safety and effectiveness of MT to the best medical care alone in the treatment of pediatric arterial ischemic stroke (AIS). It will include pediatric patients (

Abstract Background A high proportion of patients with advanced stages of medullary thyroid carcinoma (MTC) present with liver metastasis metastases. The aim of our study was to investigate the added diagnostic value of complementary gadoxetic acid-enhanced MRI to 18F-DOPA-PET/CT for liver staging in MTC. Methods Thirty-six patients (14 female, median age 55 years) with histologically confirmed MTC undergoing gadoxetic acid-enhanced liver MRI within 1 month of matching contrast-enhanced 18F-DOPA-PET/CT between 2010 and 2016 were selected for this IRB-approved retrospective study. 18F-DOPA-PET/CT and multiparametric MRI data sets were read consecutively and liver lesions were categorised on a 5-point Likert scale (1–definitely benign; 2–probably benign; 3–intermediate risk for metastasis; 4–probably metastasis; 5–definitely metastasis). It was noted if gadoxetic acid-enhanced MRI detected additional, 18F-DOPA-PET/CT-occult metastases (category 5) or if gadoxetic acid-enhanced MRI allowed for a definite classification (categories 1 and 5) of lesions for which 18F-DOPA-PET/CT remained inconclusive (categories 2–4). Follow-up PET/CT and MRI examinations were used as a reference standard. Results A total of 207 liver lesions (18F-DOPA-PET/CT 149, MRI 207; 152 metastases, 37 benign cysts, 18 hemangiomas) were analysed. Fifty-eight additional lesions were detected by MRI, of which 54 were metastases (median diameter 0.5 cm [interquartile range 0.4–0.7 cm]) occult on 18F-DOPA-PET/CT. MRI allowed for a definite lesion classification (categories 1 and 5) in 92% (190/207) whereas 18F-DOPA-PET/CT allowed for a definite lesion classification in 76% (113/149). MRI lead to a change in lesion categorisation in 14% (21/149). Conclusion Gadoxetic acid-enhanced MRI allows for a more precise liver staging in MTC patients compared to 18F-DOPA-PET/CT alone, particularly for 18F-DOPA-negative metastases and lesions

BackgroundIn certain malignancies, patients with oligometastatic disease benefit from radical ablative or surgical treatment. The SABR-COMET trial demonstrated a survival benefit for oligometastatic patients randomized to local stereotactic ablative radiation (SABR) compared to patients receiving standard care (SC) alone. Our aim was to determine the cost-effectiveness of SABR.Materials and MethodsA decision model based on partitioned survival simulations estimated costs and quality-adjusted life years (QALY) associated with both strategies in a United States setting from a health care perspective. Analyses were performed over the trial duration of six years as well as a long-term horizon of 16 years. Model input parameters were based on the SABR-COMET trial data as well as best available and most recent data provided in the published literature. An annual discount of 3% for costs was implemented in the analysis. All costs were adjusted to 2019 US Dollars according to the United States Consumer Price Index. SABR costs were reported with an average of $11,700 per treatment. Deterministic and probabilistic sensitivity analyses were performed. Incremental costs, effectiveness, and cost-effectiveness ratios (ICER) were calculated. The willingness-to-pay (WTP) threshold was set to $100,000/QALY.ResultsBased on increased overall and progression-free survival, the SABR group showed 0.78 incremental QALYs over the trial duration and 1.34 incremental QALYs over the long-term analysis. Treatment with SABR led to a marginal increase in costs compared to SC alone (SABR: $304,656; SC: $303,523 for 6 years; ICER $1,446/QALY and SABR: $402,888; SC: $350,708 for long-term analysis; ICER $38,874/QALY). Therapy with SABR remained cost-effective until treatment costs of $88,969 over the trial duration (i.e. 7.6 times the average cost). Sensitivity analysis identified a strong model impact for ongoing annual costs of oligo- and polymetastatic disease states.ConclusionOur analysis suggests that local treatment with SABR adds QALYs for patients with certain oligometastatic cancers and represents an intermediate- and long-term cost-effective treatment strategy.

BackgroundDelineation of PSMA-positive tumor volume on PET using PSMA-ligands is of highest clinical interest as changes of PSMA-PET/CT-derived whole tumor volume (WTV) have shown to correlate with treatment response in metastatic prostate cancer patients. So far, WTV estimation was performed on PET using 68Ga-labeled ligands; nonetheless, 18F-labeled PET ligands are gaining increasing importance due to advantages over 68Ga-labeled compounds. However, standardized tumor delineation methods for 18F-labeled PET ligands have not been established so far. As correlation of PET-based information and morphological extent in osseous and visceral metastases is hampered by morphological delineation, low contrast in liver tissue and movement artefacts, we correlated CT-based volume of lymph node metastases (LNM) and different PET-based delineation approaches for thresholding on 18F-PSMA-1007 PET.MethodsFifty patients with metastatic prostate cancer, 18F-PSMA-1007 PET/CT and non-bulky LNM (short-axis diameter ≥10mm) were included. Fifty LNM were volumetrically assessed on contrast-enhanced CT (volumetric reference standard). Different approaches for tumor volume delineation were applied and correlated with the reference standard: I) fixed SUV threshold, II) isocontour thresholding relative to SUVmax (SUV%), and thresholds relative to III) liver (SUVliver), IV) parotis (SUVparotis) and V) spleen (SUVspleen).ResultsA fixed SUV of 4.0 (r=0.807, r2 = 0.651, p0.05 each). Recently reported cut-offs for intraprostatic tumor delineation (isocontour 44% SUVmax, 42% SUVmax and 20% SUVmax) revealed inferior association for LNM delineation.ConclusionsA threshold of SUV 4.0 for tumor delineation showed highest association with volumetric reference standard irrespective of potential changes in PSMA-avidity of background tissues (e. g. parotis). This approach is easily applicable in clinical routine without specific software requirements. Further studies applying this approach for total tumor volume delineation are initiated.

ObjectiveThe 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.MethodsPatients 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.ResultsOne 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.ConclusionUptake 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.

Background and Purpose: Acute ischemic stroke of the anterior circulation due to large vessel occlusion (LVO) is a multifactorial process, which causes neurologic symptoms of different degree. Our aim was to examine the impact of neuromorphologic and vascular correlates as well as clinical factors on acute symptom severity in LVO stroke.Methods: We selected LVO stroke patients with known onset time from a consecutive cohort which underwent multiparametric CT including non-contrast CT, CT angiography and CT perfusion (CTP) before thrombectomy. Software-based quantification was used to calculate CTP total ischemic and ischemic core volume. Symptom severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) upon admission. Multivariable regression analysis was performed to determine independent associations of admission NIHSS with imaging and clinical parameters. Receiver operating characteristics (ROC) analyses were used to examine performance of imaging parameters to classify symptom severity.Results: We included 142 patients. Linear and ordinal regression analyses for NIHSS and NIHSS severity groups identified significant associations for total ischemic volume [β = 0.31, p = 0.01; Odds ratio (OR) = 1.11, 95%-confidence-interval (CI): 1.02–1.19], clot burden score (β = −0.28, p = 0.01; OR = 0.76, 95%-CI: 0.64–0.90) and age (β = 0.17, p = 0.04). No association was found for ischemic core volume, stroke side, collaterals and time from onset. Stroke topography according to the Alberta Stroke Program CT Score template did not display significant influence after correction for multiple comparisons. AUC for classification of the NIHSS threshold ≥6 by total ischemic volume was 0.81 (p < 0.001).Conclusions: We determined total ischemic volume, clot burden and age as relevant drivers for baseline NIHSS in acute LVO stroke. This suggests that not only mere volume but also degree of occlusion influences symptom severity. Use of imaging parameters as surrogate for baseline NIHSS reached limited performance underlining the need for combined clinical and imaging assessment in acute stroke management.

(1) Background: CT perfusion (CTP) is used to quantify cerebral hypoperfusion in acute ischemic stroke. Conventional attenuation curve analysis is not standardized and might require input from expert users, hampering clinical application. This study aims to bypass conventional tracer-kinetic analysis with an end-to-end deep learning model to directly categorize patients by stroke core volume from raw, slice-reduced CTP data. (2) Methods: In this retrospective analysis, we included patients with acute ischemic stroke due to proximal occlusion of the anterior circulation who underwent CTP imaging. A novel convolutional neural network was implemented to extract spatial and temporal features from time-resolved imaging data. In a classification task, the network categorized patients into small or large core. In ten-fold cross-validation, the network was repeatedly trained, evaluated, and tested, using the area under the receiver operating characteristic curve (ROC-AUC). A final model was created in an ensemble approach and independently validated on an external dataset. (3) Results: 217 patients were included in the training cohort and 23 patients in the independent test cohort. Median core volume was 32.4 mL and was used as threshold value for the binary classification task. Model performance yielded a mean (SD) ROC-AUC of 0.72 (0.10) for the test folds. External independent validation resulted in an ensembled mean ROC-AUC of 0.61. (4) Conclusions: In this proof-of-concept study, the proposed end-to-end deep learning approach bypasses conventional perfusion analysis and allows to predict dichotomized infarction core volume solely from slice-reduced CTP images without underlying tracer kinetic assumptions. Further studies can easily extend to additional clinically relevant endpoints.

Objectives Endovascular therapy (EVT) significantly improves clinical outcomes in patients with acute ischaemic stroke (AIS), while the time of EVT initiation after stroke onset influences both patient clinical outcomes and healthcare costs. This study determined the impact of EVT treatment delay on cost effectiveness of EVT in the Singapore healthcare setting.Design A short-term decision tree and long-term Markov health state transition model was constructed. For each time window of symptom onset to EVT, the probability of receiving EVT or non-EVT treatment was varied, thereby varying clinical outcomes (modified Rankin Scale scores), short-term costs and long-term modelled (lifetime) costs; all of which were used in calculating an incremental cost-effectiveness ratio of EVT vs non-EVT treatment. Clinical outcomes and cost data were derived from clinical trials, literature, expert opinion, electronic medical records and community-based surveys from Singapore. Deterministic one-way and probabilistic sensitivity analyses were performed to assess the uncertainty of the model. The willingness to pay for per quality-adjusted life-year (QALY) was set to Singapore $50 000 (US$36 500).Setting Singapore healthcare perspective.Participants The model included patients with AIS in Singapore.Interventions EVT performed within 6 hours of stroke onset.Outcome measures The model estimated incremental cost-effectiveness ratios (ICERs) and net monetary benefits (NMB) for EVT versus non-EVT treatment, varied by time from symptom onset to time of treatment.Results EVT performed between 61 min and 120 min after the stroke onset was most cost-effective time window to perform EVT in the Singapore population, with an ICER of Singapore $7197 per QALY (US$5254) for performing EVT at 61–120 min versus 121–180 min. The resulting incremental NMB associated with receipt of EVT at the earlier time point is Singapore $39 827 (US$29 074) per patient at the willingness-to-pay threshold of Singapore $50 000. Each hour delay in EVT resulted in an average loss of 0.54 QALYs and 195.35 healthy days, with an average net monetary loss of Singapore $26 255 (US$19 166).Conclusions From the Singapore healthcare perspective, although EVT is more expensive than alternative treatments in the short term, the lifetime ICER is below the willingness-to-pay threshold. Thus, healthcare policies and procedures should aim to improve efficiency of pre-hospital and in-hospital workflow processes to reduce the onset-to-puncture duration.

Background: PSMA-based alpha therapy using 225Ac-PSMA-I&T provides treatment for metastatic castration-resistant prostate cancer (mCRPC), even after the failure of 177Lu-PSMA radioligand therapy (RLT). In clinical routine, the total tumor volume (TTV) on PSMA PET impacts therapy outcomes and plays an increasing role in mCRPC patients. Hence, we aimed to assess TTV and its changes during 225Ac-PSMA-I&T RLT. Methods: mCRPC patients undergoing RLT with 225Ac-PSMA-I&T with available 18F-PSMA-1007 PET/CT prior to therapy initiation were included. TTV was assessed in all patients using established cut-off values. Image derived, clinical and biochemistry parameters (PSA, LDH, AP, pain score) were analyzed prior to and after two cycles of 225Ac-PSMA. Changes in TTV and further parameters were directly compared and then correlated with established response criteria, such as RECIST 1.1 or mPERCIST. Results: 13 mCRPC patients were included. The median overall survival (OS) was 10 months. Prior to 225Ac-PSMA RLT, there was no significant correlation between TTV with other clinical parameters (p > 0.05 each). Between short-term survivors (STS, p = 0.592 & p = 0.286, respectively), whereas AP was significantly lower in the LTS (p = 0.029). A total of 7/13 patients completed two cycles and underwent a follow-up 18F-PSMA-1007 PET/CT. Among these patients, there was a significant decrease in TTV (median 835 vs. 201 mL, p = 0.028) and PSA (median 687 ng/dL vs. 178 ng/dL, p = 0.018) after two cycles of 225Ac-PSMA RLT. Here, percentage changes of TTV after two cycles showed no direct correlation to all other clinical parameters (p > 0.05 each). In two patients, new PET-avid lesions were detected on 18F-PSMA-1007 PET/CT. However, TTV and PSA were decreasing or stable. Conclusion: PET-derived assessment of TTV is an easily applicable imaging biomarker independent of other established parameters prior to 225Ac-PSMA RLT in these preliminary follow-up data. Even after the failure of 177Lu-PSMA, patients with extensive TTV seem to profit from RLT. All but one patient who was eligible for ≥2 cycles of 225Ac-PSMA-RLT demonstrated drastic TTV decreases without direct correlation to other biomarkers, such as serum PSA changes. Changes in TTV might hence improve the response assessment compared to standard classifiers by reflecting the current tumor load independent of the occurrence of new lesions.

Background: Red blood cells (RBC) scintigraphy can be used not only for detection of bleeding sites, but also of spleen tissue. However, there is no established quantitative readout. Therefore, we investigated uptake in suspected splenic lesions in direct quantitative correlation to sites of physiologic uptake in order to objectify the readout. Methods: 20 patients with Tc-99m-labelled RBC scintigraphy and SPECT/low-dose CT for assessment of suspected splenic tissue were included. Lesions were rated as vital splenic or non-splenic tissue, and uptake and physiologic uptake of bone marrow, pancreas, and spleen were then quantified using a volume-of-interest based approach. Hepatic uptake served as a reference. Results: The median uptake ratio was significantly higher in splenic (2.82 (range, 0.58–24.10), n = 47) compared to other lesions (0.49 (0.01–0.83), n = 7), p < 0.001, and 5 lesions were newly discovered. The median pancreatic uptake was 0.09 (range 0.03–0.67), bone marrow 0.17 (0.03–0.45), and orthotopic spleen 14.45 (3.04–29.82). Compared to orthotopic spleens, the pancreas showed lowest uptake (0.09 vs. 14.45, p = 0.004). Based on pancreatic uptake we defined a cutoff (0.75) to distinguish splenic from other tissues. Conclusion: As the uptake in extra-splenic regions is invariably low compared to splenules, it can be used as comparator for evaluating suspected splenic tissues.

Abstract Background Focal 68Ga-DOTATATE PET lesions within the myocardium of neuroendocrine tumor (NET) patients are observed in clinical practice. We determined the frequency and characteristics of lesions that are consistent with cardiac metastasis and assessed the lesion detection rate of conventional imaging. Methods 629 patients who underwent 68Ga-DOTATATE PET-CT at a supraregional comprehensive cancer center on NET were included from a consecutive registry. Inclusion criteria were: (1) focal 68Ga-DOTATATE tracer uptake within the myocardium in more than two sequential PET exams, and (2) contrast-enhanced CT. To determine the diagnostic accuracy of conventional CT imaging, a case-control cohort with a ratio of 1:3 was used. PET and CT were independently analyzed by two blinded readers. Cohen’s κ was assessed for interreader agreement. Descriptive statistics were applied for frequencies and characteristics and group comparisons were analyzed using the Fisher’s exact test. Results The prevalence of myocardial metastases related to the registry was 2.4% (15 of 629 NET patients fulfilling the inclusion criteria), for a total of 21 myocardial 68Ga-DOTATATE foci detected. Myocardial lesions were most frequently located in the left ventricle (43%) and the septum (43%). No patient demonstrated a pericardial effusion. Patients with myocardial metastases did not differ in demographics, tumor grading, disease stage or circulating tumor markers compared to the overall registry (all p > 0.05). Higher Ki67-Indices were observed (p = 0.049) for patients with myocardial metastases. Interreader agreement for PET assessment was excellent (Cohen’s κ = 1.0). CT reading showed a sensitivity of 19% (95% confidence interval: 6–43%) at a specificity of 100% (95% confidence interval: 90–100%). Conclusions 68Ga-DOTATATE PET enables detection of myocardial metastatic lesions in NET patients. In contrast, standard morphologic CT imaging provides very limited sensitivity.

(1) Background: Respiratory insufficiency with acute respiratory distress syndrome (ARDS) and multi-organ dysfunction leads to high mortality in COVID-19 patients. In times of limited intensive care unit (ICU) resources, chest CTs became an important tool for the assessment of lung involvement and for patient triage despite uncertainties about the predictive diagnostic value. This study evaluated chest CT-based imaging parameters for their potential to predict in-hospital mortality compared to clinical scores. (2) Methods: 89 COVID-19 ICU ARDS patients requiring mechanical ventilation or continuous positive airway pressure mask ventilation were included in this single center retrospective study. AI-based lung injury assessment and measurements indicating pulmonary hypertension (PA-to-AA ratio) on admission CT, oxygenation indices, lung compliance and sequential organ failure assessment (SOFA) scores on ICU admission were assessed for their diagnostic performance to predict in-hospital mortality. (3) Results: CT severity scores and PA-to-AA ratios were not significantly associated with in-hospital mortality, whereas the SOFA score showed a significant association (p < 0.001). In ROC analysis, the SOFA score resulted in an area under the curve (AUC) for in-hospital mortality of 0.74 (95%-CI 0.63–0.85), whereas CT severity scores (0.53, 95%-CI 0.40–0.67) and PA-to-AA ratios (0.46, 95%-CI 0.34–0.58) did not yield sufficient AUCs. These results were consistent for the subgroup of more critically ill patients with moderate and severe ARDS on admission (oxygenation index

Abstract Background The purpose of the study was to investigate a novel BRAF and CDK 4/6 inhibitor combination therapy in a murine model of BRAF-V600-mutant human melanoma monitored by 18F–FDG-PET/CT and diffusion-weighted MRI (DW-MRI). Methods Human BRAF-V600-mutant melanoma (A375) xenograft-bearing balb/c nude mice (n = 21) were imaged by 18F–FDG-PET/CT and DW-MRI before (day 0) and after (day 7) a 1-week BRAF and CDK 4/6 inhibitor combination therapy (n = 12; dabrafenib, 20 mg/kg/d; ribociclib, 100 mg/kg/d) or placebo (n = 9). Animals were scanned on a small animal PET after intravenous administration of 20 MBq 18F–FDG. Tumor glucose uptake was calculated as the tumor-to-liver-ratio (TTL). Unenhanced CT data sets were subsequently acquired for anatomic coregistration. Tumor diffusivity was assessed by DW-MRI using the apparent diffusion coefficient (ADC). Anti-tumor therapy effects were assessed by ex vivo immunohistochemistry for validation purposes (microvascular density – CD31; tumor cell proliferation – Ki-67). Results Tumor glucose uptake was significantly suppressed under therapy (∆TTLTherapy − 1.00 ± 0.53 vs. ∆TTLControl 0.85 ± 1.21; p