Patient eligibility for trials with imaging response assessment at the time of molecular tumor board presentation.

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 (< 55%). In case of MD, the measurable lesions were representative of the overall tumor burden in the vast majority of cases (94%). CONCLUSION: Approximately one third of cancer patients with advanced solid malignancies are not eligible for treatment response assessment in trials with endpoints ORR or DOR at the time of MTB presentation. The rate of patients eligible for trials with imaging endpoints differs significantly based on the underlying malignancy and should be taken under consideration during the planning of new precision oncology trials.

Endovascular thrombectomy is cost-saving in patients with acute ischemic stroke with large infarct.

Objective: Endovascular 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. Methods: Costs 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. Results: Endovascular 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. Conclusion: EVT 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.

Ultrahigh-Spatial-Resolution Photon-counting Detector CT Angiography of Coronary Artery Disease for Stenosis Assessment.

Background Coronary CT angiography is a first-line test in coronary artery disease but is limited by severe calcifications. Photon-counting-detector (PCD) CT improves spatial resolution. Purpose To investigate the effect of improved spatial resolution on coronary stenosis assessment and reclassification. Materials and Methods Coronary stenoses were evaluated prospectively in a vessel phantom (in vitro) containing two stenoses (25%, 50%), and retrospectively in patients (in vivo) who underwent ultrahigh-spatial-resolution cardiac PCD CT (from July 2022 to April 2023). Images were reconstructed at standard resolution (section thickness, 0.6 mm; increment, 0.4 mm; Bv44 kernel), high spatial resolution (section thickness, 0.4 mm; increment, 0.2 mm; Bv44 kernel), and ultrahigh spatial resolution (section thickness, 0.2; increment, 0.1 mm; Bv64 kernel). Percentages of diameter stenosis (DS) were compared between reconstructions. In vitro values were compared with the manufacturer specifications of the phantom and patient results were assessed regarding effects on Coronary Artery Disease Reporting and Data System (CAD-RADS) reclassification. Results The in vivo sample included 114 patients (mean age, 68 years ± 9 [SD]; 71 male patients). In vitro percentage DS measurements were more accurate with increasing spatial resolution for both 25% and 50% stenoses (mean bias for standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 10.1%, 8.0%, and 2.3%; P < .001). In vivo results confirmed decreasing median percentage DS with increasing spatial resolution for calcified stenoses (n = 161) (standard resolution, high spatial resolution, and ultrahigh spatial resolution, respectively: 41.5% [IQR, 27.3%-58.2%], 34.8% [IQR, 23.7%-55.1%], and 26.7% [IQR, 18.6%-44.3%]; P < .001), whereas noncalcified (n = 13) and mixed plaques (n = 19) did not show evidence of a difference (P ≥ .88). Ultrahigh-spatial-resolution reconstructions led to reclassification of 62 of 114 (54.4%) patients to lower CAD-RADS category than that assigned using standard resolution. Conclusion In vivo and in vitro coronary stenosis assessment improved for calcified stenoses by using ultrahigh-spatial-resolution PCD CT reconstructions, leading to lower percentage DS compared with standard resolution and clinically relevant rates of reclassification. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by McCollough in this issue.

Radiological age assessment based on clavicle ossification in CT: enhanced accuracy through deep learning.

BACKGROUND: Radiological age assessment using reference studies is inherently limited in accuracy due to a finite number of assignable skeletal maturation stages. To overcome this limitation, we present a deep learning approach for continuous age assessment based on clavicle ossification in computed tomography (CT). METHODS: Thoracic CT scans were retrospectively collected from the picture archiving and communication system. Individuals aged 15.0 to 30.0 years examined in routine clinical practice were included. All scans were automatically cropped around the medial clavicular epiphyseal cartilages. A deep learning model was trained to predict a person's chronological age based on these scans. Performance was evaluated using mean absolute error (MAE). Model performance was compared to an optimistic human reader performance estimate for an established reference study method. RESULTS: The deep learning model was trained on 4,400 scans of 1,935 patients (training set: mean age = 24.2 years ± 4.0, 1132 female) and evaluated on 300 scans of 300 patients with a balanced age and sex distribution (test set: mean age = 22.5 years ± 4.4, 150 female). Model MAE was 1.65 years, and the highest absolute error was 6.40 years for females and 7.32 years for males. However, performance could be attributed to norm-variants or pathologic disorders. Human reader estimate MAE was 1.84 years and the highest absolute error was 3.40 years for females and 3.78 years for males. CONCLUSIONS: We present a deep learning approach for continuous age predictions using CT volumes highlighting the medial clavicular epiphyseal cartilage with performance comparable to the human reader estimate.

Diffusion-weighted MRI (DWI) for assessment of response to high-dose-rate CT-guided brachytherapy (HDR-BT) of hepatocellular carcinoma.

BACKGROUND: High-dose-rate computed tomography (CT)-guided brachytherapy (HDR-BT) has shown promising results in patients with hepatocellular carcinoma (HCC). While growing evidence shows clear limitations of mRECIST, diffusion-weighted imaging (DWI) has relevant potential in improving the response assessment. PURPOSE: To assess whether DWI allows evaluation of short- and long-term tumor response in patients with HCC after HDR-BT. MATERIAL AND METHODS: A total of 22 patients with 11 non-responding HCCs (NR-HCC; local tumor recurrence within two years) and 24 responding HCCs (R-HCC; follow-up at least two years) were included in this retrospective bi-center study. HCCs were treated with HDR-BT and patients underwent pre- and post-interventional magnetic resonance imaging (MRI). Analyses of DWI were evaluated and compared between pre-interventional MRI, 1.follow-up after 3 months and 2.follow-up at the time of the local tumor recurrence (in NR-HCC) or after 12 months (in R-HCC). RESULTS: ADCmean of R-HCC increased significantly after HDR-BT on the first and second follow-up (ADCmean: 0.87 ± 0.18 × 10-3 mm2/s [pre-interventional]: 1.14 ± 0.23 × 10-3 mm2/s [1. post-interventional]; 1.42 ± 0.32 × 10-3 mm2/s [2. post-interventional]; P < 0.001). ADCmean of NR-HCC did not show a significant increase from pre-intervention to 1. post-interventional MRI (ADCmean: 0.85 ± 0.24 × 10-3 mm2/s and 1.00 ± 0.30 × 10-3 mm2/s, respectively; P = 0.131). ADCmean increase was significant between pre-intervention and 2. follow-up (ADCmean: 1.03 ± 0.19 × 10-3 mm2/s; P = 0.018). There was no significant increase of ADCmean between the first and second follow-up. There was, however, a significant increase of ADCmin after 12 months (ADCmin: 0.87 ± 0.29 × 10-3 mm2/s) compared to pre-interventional MRI and first follow-up (P < 0.005) only in R-HCC. CONCLUSION: The tumor response after CT-guided HDR-BT was associated with a significantly higher increase in ADCmean and ADCmin in short- and long-term follow-up.

Cost-effectiveness of endovascular treatment versus best medical management in basilar artery occlusion stroke: A U.S. healthcare perspective.

INTRODUCTION: Two recent studies showed clinical benefit for endovascular treatment (EVT) in basilar artery occlusion (BAO) stroke up to 12 h (ATTENTION) and between 6 and 24 h from onset (BAOCHE). Our aim was to investigate the cost-effectiveness of EVT from a U.S. healthcare perspective. MATERIALS AND METHODS: Clinical input data were available for both trials, which were analyzed separately. A decision model was built 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 from a healthcare and a societal perspective. Incremental cost-effectiveness ratios (ICER) were calculated, deterministic (DSA) and probabilistic (PSA) sensitivity analyses were performed. RESULTS: EVT in addition to best medical management (BMM) resulted in additional lifetime costs of $32,063 in the ATTENTION trial and lifetime cost savings of $7690 in the BAOCHE trial (societal perspective). From a healthcare perspective, EVT led to incremental costs and effectiveness of $37,389 and 2.0 QALYs (ATTENTION) as well as $3516 and 1.9 QALYs (BAOCHE), compared to BMM alone. The ICER values were $-4052/QALY (BAOCHE) and $15,867/QALY (ATTENTION) from a societal perspective. In each trial, PSA showed EVT to be cost-effective in most calculations (99.9%) for a willingness-to-pay threshold of $100,000/QALY. Cost of EVT and age at stroke represented the greatest impact on the ICER. DISCUSSION: From an economic standpoint with a lifetime horizon, EVT in addition to BMM is estimated to be highly effective and cost-effective in BAO stroke.

Is PSMA PET/CT cost-effective for the primary staging in prostate cancer? First results for European countries and the USA based on the proPSMA trial.

PURPOSE: The proPSMA trial at ten Australian centers demonstrated increased sensitivity and specificity for PSMA PET/CT compared to conventional imaging regarding metastatic status in primary high-risk prostate cancer patients. A cost-effectiveness analysis showed benefits of PSMA PET/CT over conventional imaging for the Australian setting. However, comparable data for other countries are lacking. Therefore, we aimed to verify the cost-effectiveness of PSMA PET/CT in several European countries as well as the USA. METHODS: Clinical data on diagnostic accuracy were derived from the proPSMA trial. Costs for PSMA PET/CT and conventional imaging were taken from reimbursements of national health systems and individual billing information of selected centers in Belgium, Germany, Italy, the Netherlands, and the USA. For comparability, scan duration and the decision tree of the analysis were adopted from the Australian cost-effectiveness study. RESULTS: In contrast to the Australian setting, PSMA PET/CT was primarily associated with increased costs in the studied centers in Europe and the USA. Mainly, the scan duration had an impact on the cost-effectiveness. However, costs for an accurate diagnosis using PSMA PET/CT seemed reasonably low compared to the potential consequential costs of an inaccurate diagnosis. CONCLUSION: We assume that the use of PSMA PET/CT is appropriate from a health economic perspective, but this will need to be verified by a prospective evaluation of patients at initial diagnosis.

Automated localization of the medial clavicular epiphyseal cartilages using an object detection network: a step towards deep learning-based forensic age assessment.

BACKGROUND: Deep learning is a promising technique to improve radiological age assessment. However, expensive manual annotation by experts poses a bottleneck for creating large datasets to appropriately train deep neural networks. We propose an object detection approach to automatically annotate the medial clavicular epiphyseal cartilages in computed tomography (CT) scans. METHODS: The sternoclavicular joints were selected as structure-of-interest (SOI) in chest CT scans and served as an easy-to-identify proxy for the actual medial clavicular epiphyseal cartilages. CT slices containing the SOI were manually annotated with bounding boxes around the SOI. All slices in the training set were used to train the object detection network RetinaNet. Afterwards, the network was applied individually to all slices of the test scans for SOI detection. Bounding box and slice position of the detection with the highest classification score were used as the location estimate for the medial clavicular epiphyseal cartilages inside the CT scan. RESULTS: From 100 CT scans of 82 patients, 29,656 slices were used for training and 30,846 slices from 110 CT scans of 110 different patients for testing the object detection network. The location estimate from the deep learning approach for the SOI was in a correct slice in 97/110 (88%), misplaced by one slice in 5/110 (5%), and missing in 8/110 (7%) test scans. No estimate was misplaced by more than one slice. CONCLUSIONS: We demonstrated a robust automated approach for annotating the medial clavicular epiphyseal cartilages. This enables training and testing of deep neural networks for age assessment.

Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer.

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.

Cost-effectiveness of Response-Adapted De-escalation of Immunotherapy in Advanced Melanoma.

Importance: Combination immunotherapy with nivolumab and ipilimumab has markedly improved outcomes for patients with advanced melanoma. However, these therapies pose a considerable financial burden to both patients and the health care system. The ADAPT-IT trial demonstrated comparable progression-free and overall survival for patients with response-adapted ipilimumab discontinuation compared with standard of care (SOC). Objective: To determine the cost-effectiveness of ipilimumab discontinuation for patients with interim imaging-confirmed tumor response in the treatment of advanced melanoma. Design, Setting, and Participants: This cost-effectiveness analysis was performed using data from the ADAPT-IT (follow-up of 33 months) and CheckMate 067 (follow-up of 6.5 years) trials, as well as published literature over the ADAPT-IT trial duration of 33 months. The analysis was performed in a US setting from a US-payer perspective, and the willingness-to-pay (WTP) threshold was set at $100 000/quality-adjusted life-year (QALY). A total of 355 patients with previously untreated melanoma (unresectable stage III or IV metastatic melanoma) were included. Exposure: Response-adapted ipilimumab discontinuation compared with SOC therapy. Main Outcomes and Measures: The primary outcomes of the CheckMate trial were overall survival and progression-free survival, while that of ADAPT-IT was objective response. This informed a decision model to estimate lifetime costs and QALYs associated with both strategies. Incremental cost, effectiveness, and cost-effectiveness ratio were assessed. Sensitivity and scenario analyses were performed to account for variability in trials and input parameters. Results: Of the 355 patients included in the analysis, 41 patients were from the ADAPT-IT trial (median age, 65 years; 28 [68%] male) and 314 patients from the CheckMate 067 trial (median age, 61 years; 206 [66%] male). Response-adapted treatment was the cost-effective option in 94.0% of scenarios based on Monte Carlo simulations, with a dominant incremental cost-effectiveness ratio and an incremental net monetary benefit of $28 849 compared with SOC therapy. Cost savings were estimated at $19 891 per patient compared with SOC. In scenario analyses, current SOC was only considered as a cost-effective option under best survival assumptions and if the willingness-to-pay threshold exceeded $630 000/QALY. Conclusions and Relevance: This economic evaluation demonstrated that response-adapted treatment de-escalation in patients with advanced melanoma may lead to considerable savings in health care costs and could represent the most cost-effective strategy across various resource settings. Future trials should aim to provide further evidence on noninferiority.

Treatment Assessment of pNET and NELM after Everolimus by Quantitative MRI Parameters.

Assessment of treatment response to targeted therapies such as everolimus is difficult, especially in slow-growing tumors such as NETs. In this retrospective study, 17 patients with pancreatic neuroendocrine tumors (pNETs) and hepatic metastases (NELMs) (42 target lesions) who received everolimus were analyzed. Intralesional signal intensities (SI) of non-contrast T1w, T2w and DCE imaging, and apparent diffusion coefficients (ADCmean and ADCmin) of DWI, were measured on baseline and first follow-up MRI after everolimus initiation. Response assessment was categorized according to progression-free survival (PFS), with responders (R) showing a PFS of ≥11 months. ADCmin of NELMs decreased in Rs whereas it increased in non-responders (NR). Percentual changes of ADCmin and ADCmean differed significantly between response groups (p < 0.03). By contrast, ADC of the pNETs tended to increase in Rs, while there was no change in NRs. Tumor-to-liver (T/L) ratio of T1 SI of NELMs increased in Rs and decreased in NRs, and percentual changes differed significantly between response groups (p < 0.02). T1 SI of the pNETs tended to decrease in Rs and increase in Ns. The quotient of pretherapeutic and posttherapeutic ADCmin values (DADCmin) and length of everolimus treatment showed significant association with PFS in univariable Cox analysis. In conclusion, quantitative MRI, especially DWI, seems to allow treatment assessment of pNETs with NELMs under everolimus. Interestingly, the responding NELMs showed decreasing ADC values, and there might be an opposite effect on ADC and T1 SI between NELMs and pNETs.

Lymphoma tumor burden before chimeric antigen receptor T-Cell treatment: RECIL vs. Lugano vs. metabolic tumor assessment.

Purpose: High 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 methods: In 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. Results: 34 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, p<0.001 and ρ=0.741, p<0.001), with lowest correlation for extranodal TBRECIL with TBMTV (ρ=0.660, p<0.001). Stratification of PFS was strongest by total TBMTV>50% (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). Conclusion: Pre-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.

Semi-Automatic MRI Feature Assessment in Small- and Medium-Volume Benign Prostatic Hyperplasia after Prostatic Artery Embolization.

(1) Background: To assess the treatment response of benign prostatic syndrome (BPS) following prostatic artery embolization (PAE) using a semi-automatic software analysis of magnetic resonance imaging (MRI) features and clinical indexes. (2) Methods: Prospective, monocenter study of MRI and clinical data of n = 27 patients with symptomatic BPS before and (1, 6, 12 months) after PAE. MRI analysis was performed using a dedicated semi-automatic software for segmentation of the central and the total gland (CG, TG), respectively; signal intensities (SIs) of T1-weighted (T1w), T2-weighted (T2w), and diffusion-weighted images (DWI), as well as intravesical prostatic protrusion (IPP) and prostatic volumes (CGV, TGV), were evaluated at each time point. The semi-automatic assessed TGV was compared to conventional TGV by an ellipse formula. International prostate symptom score (IPSS) and international consultation on incontinence questionnaire−urinary incontinence short form (ICIQ-UI SF) questionnaires were used as clinical indexes. Statistical testing in the form of ANOVA, pairwise comparisons using Bonferroni correction, and multiple linear correlations, were conducted using SPSS. (3) Results: TGV was significantly reduced one, six, and 12 months after PAE as assessed by the semi-automatic approach and conventional ellipse formula (p = 0.005; p = 0.025). CGV significantly decreased after one month (p = 0.038), but showed no significant differences six and 12 months after PAE (p = 0.191; p = 0.283). IPP at baseline was demonstrated by 25/27 patients (92.6%) with a significant decrease one, six, and 12 months after treatment (p = 0.028; p = 0.010; p = 0.008). Significant improvement in IPSS and ICIQ-UI SF (p = 0.002; p = 0.016) after one month correlated moderately with TGV reduction (p = 0.031; p = 0.05, correlation coefficients 0.52; 0.69). Apparent diffusion coefficient (ADC) values of CG significantly decreased one month after embolization (p < 0.001), while there were no significant differences in T1w and T2w SIs before and after treatment at each time point. (4) Conclusions: The semi-automatic approach is appropriate for the assessment of volumetric and morphological changes in prostate MRI following PAE, able to identify significantly different ADC values post-treatment without the need for manual identification of infarct areas. Semi-automatic measured TGV reduction is significant and comparable to the TGV calculated by the conventional ellipse formula, confirming the clinical response after PAE.

Cost-Effectiveness of Endovascular Thrombectomy in Childhood Stroke: An Analysis of the Save ChildS Study.

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.

Early tumor shrinkage and response assessment according to mRECIST predict overall survival in hepatocellular carcinoma patients under sorafenib.

BACKGROUND: The aim of this study was to explore the relationship between follow-up imaging characteristics and overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients under sorafenib treatment. METHODS: Associations between OS and objective response (OR) by mRECIST or early tumor shrinkage (ETS; ≥20% reduction in enhancing tumor diameter at the first follow-up imaging) were analyzed in HCC patients treated with sorafenib within a multicenter phase II trial (SORAMIC). 115 patients were included in this substudy. The relationship between survival and OR or ETS were explored. Landmark analyses were performed according to OR at fixed time points. Cox proportional hazards models with OR and ETS as a time-dependent covariate were used to compare survival with factors known to influence OS. RESULTS: The OR rate was 29.5%. Responders had significantly better OS than non-responders (median 30.3 vs. 11.4 months; HR, 0.38 [95% CI, 0.22-0.63], p < 0.001), and longer progression-free survival (PFS; median 10.1 vs. 4.3 months, p = 0.015). Patients with ETS ≥ 20% had longer OS (median 22.1 vs. 11.4 months, p = 0.002) and PFS (median 8.0 vs. 4.3 months, p = 0.034) than patients with ETS < 20%. Besides OR and ETS, male gender, lower bilirubin and ALBI grade were associated with improved OS in univariate analysis. Separate models of multivariable analysis confirmed OR and ETS as independent predictors of OS. CONCLUSION: OR according to mRECIST and ETS in patients receiving sorafenib treatment are independent prognostic factors for OS. These parameters can be used for assessment of treatment benefit and optimal treatment sequencing in patients with advanced HCC.

Apparent diffusion coefficients (ADC) in response assessment of transarterial radioembolization (TARE) for liver metastases of neuroendocrine tumors (NET): a feasibility study.

BACKGROUND: In patients with hepatic neuroendocrine tumors (NETs) locoregional therapies such as transarterial radioembolization (TARE) are increasingly applied. Response evaluation remains challenging and previous studies assessing response with diffusion-weighted imaging (DWI) have been inconclusive. PURPOSE: To perform a feasibility study to evaluate if response assessment with quantitative apparent diffusion coefficient (ADC) in patients with liver metastases of NETs after TARE will be possible. MATERIAL AND METHODS: Retrospectively, 43 patients with 120 target lesions who obtained abdominal magnetic resonance imaging (MRI) with DWI 39±28 days before and 74±46 days after TARE were included. Intralesional ADC (ADCmin, ADCmax, and ADCmean) were measured for a maximum number of three lesions per patient on baseline and post-interventional DWI. Tumor response was categorized according to RECIST 1.1 and mRECIST. RESULTS: TARE resulted in partial remission (PR) in 23% (63%), in stable disease (SD) in 73% (23%), in progressive disease (PD) in 5% (7%) and in complete response (CR) in 0% (1%) according to RECIST 1.1 (mRECIST, respectively). ADC values increased significantly (P<0.005) after TARE in the PR group whereas there was no significant change in the PD group. Post-therapeutic ADC values of SD lesions increased significantly when evaluated by RECIST 1.1 but not if evaluated by mRECIST. Percentual changes of ADCmean values were slightly higher for responders compared to non-responders (P<0.05). CONCLUSION: ADC values seem to represent an additional marker for treatment response evaluation after TARE in patients with secondary hepatic NET. A conclusive study seems feasible though patient-based evaluation and overall survival and progression free survival as alternate primary endpoints should be considered.

Cost-effectiveness of short-protocol emergency brain MRI after negative non-contrast CT for minor stroke detection.

OBJECTIVES: To investigate the cost-effectiveness of supplemental short-protocol brain MRI after negative non-contrast CT for the detection of minor strokes in emergency patients with mild and unspecific neurological symptoms. METHODS: The economic evaluation was centered around a prospective single-center diagnostic accuracy study validating the use of short-protocol brain MRI in the emergency setting. A decision-analytic Markov model distinguished the strategies "no additional imaging" and "additional short-protocol MRI" for evaluation. Minor stroke was assumed to be missed in the initial evaluation in 40% of patients without short-protocol MRI. Specialized post-stroke care with immediate secondary prophylaxis was assumed for patients with detected minor stroke. Utilities and quality-of-life measures were estimated as quality-adjusted life years (QALYs). Input parameters were obtained from the literature. The Markov model simulated a follow-up period of up to 30 years. Willingness to pay was set to $100,000 per QALY. Cost-effectiveness was calculated and deterministic and probabilistic sensitivity analysis was performed. RESULTS: Additional short-protocol MRI was the dominant strategy with overall costs of $26,304 (CT only: $27,109). Cumulative calculated effectiveness in the CT-only group was 14.25 QALYs (short-protocol MRI group: 14.31 QALYs). In the deterministic sensitivity analysis, additional short-protocol MRI remained the dominant strategy in all investigated ranges. Probabilistic sensitivity analysis results from the base case analysis were confirmed, and additional short-protocol MRI resulted in lower costs and higher effectiveness. CONCLUSION: Additional short-protocol MRI in emergency patients with mild and unspecific neurological symptoms enables timely secondary prophylaxis through detection of minor strokes, resulting in lower costs and higher cumulative QALYs. KEY POINTS: • Short-protocol brain MRI after negative head CT in selected emergency patients with mild and unspecific neurological symptoms allows for timely detection of minor strokes. • This strategy supports clinical decision-making with regard to immediate initiation of secondary prophylactic treatment, potentially preventing subsequent major strokes with associated high costs and reduced QALY. • According to the Markov model, additional short-protocol MRI remained the dominant strategy over wide variations of input parameters, even when assuming disproportionally high costs of the supplemental MRI scan.

Stent-graft placement for hepatic arterial bleeding: assessment of technical efficacy and clinical outcome in a tertiary care center.

BACKGROUND: To evaluate technical and clinical results of stent-graft (SG) placement for bleeding from the hepatic artery (HA). METHODS: All patients intended and treated with SG deployment for bleeding from the HA at single center from January 2012 to May 2020 were retrospectively identified, and procedural details, risk factors for rebleeding, SG occlusion and mortality were analyzed. RESULTS: Twenty-seven patients (mean age 68.8 ± 10.1) were identified, and 25 patients underwent 26 SG procedures. Twenty-four patients had recent surgery. The technical success rate was 92.8%. Three patients (3/25) had rebleeding (88% clinical success). Intensive-care need before the procedure (p = 0.013) and smaller stent-graft size (≤4 mm, p = 0.032) were related to clinical failure. Twenty-two patients had follow-up imaging. The SG maintained patency in 10 (45.4%) patients at the most recent imaging. Only placement of SG distal to the HA bifurcation (p = 0.012) was related to occlusion. The 30-day and in-hospital mortality rate after SG was 8% and 24%. In-hospital mortality was associated with the intraabdominal septic source (p = 0.010) and revision surgery (p = 0.001). CONCLUSION: Stent-grafts are effective in the emergent treatment of HA bleeding. Mortality is mainly related to the general condition of the patient, and stent-grafts offer time to treat underlying medical problems sufficiently.

68Ga-DOTATATE PET/CT and MRI with Diffusion-Weighted Imaging (DWI) in Short- and Long-Term Assessment of Tumor Response of Neuroendocrine Liver Metastases (NELM) Following Transarterial Radioembolization (TARE).

The aim of this study was to evaluate the role of SUV and ADC in assessing early response in patients with NELM following TARE. Thirty-two patients with pre- and postinterventional MRI with DWI and 68Ga-DOTATATE PET/CT were included. ADC and SUV of three target lesions and of tumor-free spleen and liver tissue were determined on baseline and first follow-up imaging, and tumor to spleen (T/S) and tumor to liver (T/L) ratios were calculated. Response was assessed by RECIST 1.1 and mRECIST on first follow-up, and long-term response was defined as hepatic progression-free survival (HPFS) over 6, 12, and <24 months. In responders, intralesional ADC values increased and SUV decreased significantly regardless of standard of reference for response assessment (mRECIST/RECIST/HPFS > 6/12/24 m). Using ROC analysis, ΔSUV T/S ratio (max/max) and ΔSUV T/L ratio (max/mean) were found to be the best and most robust metrics to correlate with longer HPFS and were superior to ΔADC. ΔT/S ratio (max/max) < 23% was identified as an optimal cut-off to discriminate patients with longer HPFS (30.2 m vs. 13.4 m; p = 0.0002). In conclusion, early percentage changes in SUV tumor-to-organ ratios on first follow-up seem to represent a prognostic marker for longer HPFS and may help in assessing therapeutic strategies.