Abstract Background Differentiation of bowel wall changes between ischemia and other causes in CT imaging can prove challenging, particularly in colon wall. Therefore, measurement of relative colon wall attenuation and contrast uptake were evaluated for aiding in diagnosis of colon ischemia. Methods CTs with inquiry for bowel ischemia were retrospectively identified. Cases involving colon ischemia or colon wall changes of other etiologies were included. Three regions of interest (ROIs) were placed in representative areas of colon wall with and without evident changes, in arterial and venous phase images, respectively. Means of the ROIs were used to calculate the relative bowel enhancement between affected and unaffected wall in each contrast phase, as well as the contrast uptake of the wall between phases. Relative enhancement and contrast uptake were compared between patients with and without ischemia. A subset of cases was reanalyzed for intra- and inter-reader comparison. Results 31 patients with and 56 patients without ischemia were included. Relative enhancement of affected to unaffected colon wall was -51.2% in arterial phase and -44.6% in venous phase images for patients with ischemia. Relative enhancement was significantly higher in patients without ischemia at -0.5% in both phases ( p < 0.001). There was no significant difference in contrast uptake of affected bowel (40.6% vs. 39.8% respectively, p = 0.67). ROC curves revealed a maximum Youden-Index at a cut-off of -37.4% (AUC: 0.818) in arterial phase to differentiate between groups. Intra-reader comparison showed a good, and inter-reader a moderate, correlation in a subset. Conclusions Objective measurement of relative colon wall attenuation between affected and unaffected areas can be an additional imaging feature to aid in identifying ischemic colon.

In this study, pre-treatment target lesion vascularisation in either contrast-enhanced (CE) CT or MRI and post-treatment lipiodol deposition in native CT scans were compared in HCC patients who underwent their first cTACE treatment. We analysed the impact of stratification according to cTACE selectivity on these correlations. Seventy-eight HCC patients who underwent their first cTACE procedure were retrospectively included. Pre-treatment tumour vascularisation in arterial contrast phase and post-treatment lipiodol deposition in native CT scans were evaluated using the qEASL (quantitative tumour enhancement) method. Correlations were analysed using scatter plots, the Pearson correlation coefficient (PCC) and linear regression analysis. Subgroup analysis was performed according to lobar, segmental and subsegmental execution of cTACE. Arterial tumour volumes in both baseline CE CT (R2 = 0.83) and CE MR (R2 = 0.82) highly correlated with lipiodol deposition after cTACE. The regression coefficient between lipiodol deposition and enhancing tumour volume was 1.39 for CT and 0.33 for MR respectively, resulting in a ratio of 4.24. After stratification according to selectivity of cTACE, the regression coefficient was 0.94 (R2 = 1) for lobar execution, 1.38 (R2 = 0.96) for segmental execution and 1.88 (R2 = 0.89) for subsegmental execution in the CE CT group. Volumetric lipiodol deposition can be used as a reference to compare different imaging modalities in detecting vital tumour volumes. That approach proved CE MRI to be more sensitive than CE CT. Selectivity of cTACE significantly impacts the respective regression coefficients which allows for an innovative approach to the assessment of technical success after cTACE with a multitude of possible applications. • Lipiodol deposition after cTACE highly correlates with pre-treatment tumour vascularisation and can be used as a reference to compare different imaging modalities in detecting vital tumour volumes. • Lipiodol deposition also correlates with the selectivity of cTACE and can therefore be used to quantify the technical success of the intervention.

Background:Established morpho-functional chest magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in people with cystic fibrosis (pwCF) using a dedicated scoring system. Functional assessment is performed using contrast-enhanced (CE) perfusion MRI. Novel matrix pencil decomposition MRI (MP-MRI) is a contrast agent-free alternative, but further validation of this technique is needed. Objectives:The aim of this study was to evaluate the applicability of the validated morpho-functional chest MRI score for CE perfusion and MP perfusion MRI in a multireader approach. Methods:Twenty-seven pwCF (mean age 20.8 years, range 8.4-45.7 years) underwent morpho-functional MRI including CE perfusion and MP perfusion MRI in the same examination. Nine blinded chest radiologists of different experience levels assessed lung perfusion and applied the validated chest MRI score to CE- and MP-MRI. Inter-reader agreement of perfusion scores in CE- and MP-MRI were compared with each other and with the MRI morphology score. Differences according to the readers' experience were also analyzed. Results:The CE perfusion scores were overall lower than the MP perfusion scores (6.2 ± 3.3 vs. 6.9 ± 2.0; p < 0.05) with a strong correlation between both perfusion scores (r = 0.74; p < 0.01). The intraclass correlation coefficient (ICC) as measure for inter-reader agreement was good and significant for both perfusion scores, but higher for the CE perfusion score (0.75, p < 0.001) than for MP perfusion scores (0.61, p < 0.001). The Bland-Altman analysis revealed a difference in CE and MP perfusion scores with more extreme values in CE perfusion scores compared to MP perfusion scores (r = 0.62, p < 0.001). The morphology score showed a moderate to good correlation with the CE perfusion score (r = 0.73, p < 0.01) and the MP perfusion score (r = 0.55, p < 0.01). We did not find a difference in scoring according to the radiological experience level. Conclusion:The established chest MRI score can be applied both to validated CE and novel MP perfusion MRI with a good interreader reliability. The remaining difference between CE and MP-MRI scores may be explained by a lack of routine in visual analysis of MP-MRI and may favor an automated analysis for use of MP-MRI as a noninvasive outcome measure.

Abstract Background To investigate the capacity of 99mTc-labeled 1-thio-β-D-glucose (1-TG) and 5-thio-D-glucose (5-TG) to act as a marker for glucose consumption in tumor cells in vivo as well as to evaluate the biodistribution of 1-TG and 5-TG. We investigated the biodistribution, including tumor uptake, of 1-TG and 5-TG at various time points after injection (0.5, 2 and 4 h) in human colorectal carcinoma (HCT-116) and human lung adenocarcinoma (A549) xenograft bearing nude mice (N = 4 per tracer and time point). Results Ex vivo biodistribution studies revealed a moderate uptake with a maximum tumor-to-muscle ratio of 4.22 ± 2.7 and 2.2 ± 1.3 (HCT-116) and of 3.2 ± 1.1 and 4.1 ± 1.3 (A549) for 1-TG and 5-TG, respectively, with a peak at 4 h for 1-TG and 5-TG. Biodistribution revealed a significantly higher uptake compared to blood in kidneys (12.18 ± 8.77 and 12.69 ± 8.93%ID/g at 30 min) and liver (2.6 ± 2.8%ID/g) for 1-TG and in the lung (7.24 ± 4.1%ID/g), liver (6.38 ± 2.94%ID/g), and kidneys (4.71 ± 1.97 and 4.81 ± 1.91%ID/g) for 5-TG. Conclusions 1-TG and 5-TG showed an insufficient tumor uptake with a moderate tumor-to-muscle ratio, not reaching the levels of commonly used tracer, for diagnostic use in human colorectal carcinoma and human lung adenocarcinoma xenograft model.

Relapsed Acute Lymphoblastic Leukemia (ALL) is among the most common causes of cancer-associated deaths in children. However, little is known about the implications of deviations from ALL treatment protocols on survival rates. The present study elucidates the various characteristics of treatment deviations in children with relapsed ALL included in the ALL-REZ BFM 2002 (i.e., Relapse Berlin-Frankfurt- Münster) trial and determines their prognostic relevance for relapse and death rates. Among 687 patients, 100 were identified with treatment deviations, further classified, and examined by occurrence time, cause and type. Protocol deviation was considered a time-dependent variable and its impact on Disease Free Survival (DFS) and Overall Survival (OS) was examined using the time-dependent model Mantel Byar. Five years after the relapse diagnosis, deviations were significantly related to both inferior DFS (38

BackgroundPrevious studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration.ObjectivesTo compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF.MethodsThirty-nine clinically stable patients with CF (mean age 21.6 ± 10.7 years, range 8–45 years) prospectively underwent morpho-functional MRI including CE perfusion MRI, MP-MRI and spirometry. Two blinded chest radiologists assessed morpho-functional MRI and MP-MRI employing the validated chest MRI score. In addition, MP-MRI data were processed by automated software calculating perfusion defect percentage (QDP) and ventilation defect percentage (VDP).ResultsMP perfusion score and QDP correlated strongly with the CE perfusion score (both r = 0.81; p < 0.01). MP ventilation score and VDP showed strong inverse correlations with percent predicted FEV1 (r = −0.75 and r = −0.83; p < 0.01). The comparison of visual and automated parameters showed that both MP perfusion score and QDP, and MP ventilation score and VDP were strongly correlated (r = 0.74 and r = 0.78; both p < 0.01). Further, the MP perfusion score and MP ventilation score, as well as QDP and VDP were strongly correlated (r = 0.88 and r = 0.86; both p < 0.01).ConclusionMP-MRI detects abnormalities in lung perfusion and ventilation in patients with CF without intravenous or inhaled contrast agent application, and correlates strongly with the well-established CE perfusion MRI score and spirometry. Automated analysis of MP-MRI may serve as quantitative noninvasive outcome measure for diagnostic monitoring and clinical trials.

Prostate Imaging Reporting and Data System version 2.1 (PI-RADS) category 3 lesions are a challenge in the clinical workflow. A better detection of the infrequently occurring clinically significant prostate cancer (csPCa) in PI-RADS 3 lesions is an important objective. The purpose of this study was to evaluate if feature maps calculated from T2-weighted (T2w) 3 Tesla (3T) MRI can help detect csPCa in PI-RADS category 3 lesions. In-house biparametric 3T prostate MRI examinations acquired between January 2019 and June 2023 because of elevated prostate-specific antigen (PSA) levels were retrospectively screened. Inclusion criteria were a PI-RADS 3 lesion and available results of an ultrasound-guided targeted and systematic biopsy. Exclusion criteria were a simultaneous PI-RADS category 4 or 5 lesion and hip replacement. Target lesions with the International Society of Urological Pathology (ISUP) grade group 1 were rated clinically insignificant PCa (ciPCa) and ≥2 csPCa. This resulted in 52 patients being included in the final analysis, of whom 11 (21.1%), 8 (15.4%), and 33 (63.5%) patients had csPCa, ciPCa, and no PCa, respectively, with the latter two groups being combined as non-csPCa. Eight of the csPCas were located in the peripheral zone (PZ) and three in the transition zone (TZ). In the non-csPCa group, 29 were located in the PZ and 12 in the TZ. Target lesions were marked with volumes of interest (VOIs) on axial T2w images. Axial T2w images were then converted to 93 feature maps. VOIs were copied into the maps, and feature quantity was retrieved directly. Features were tested for significant differences with the Mann–Whitney U-test. Univariate models for single feature performance and bivariate models implementing PSA density (PSAD) were calculated. Ten map-derived features differed significantly between the csPCa and non-csPCa groups (AUCs: 0.70–0.84). The diagnostic performance for TZ lesions (AUC: 0.83–1.00) was superior to PZ lesions (AUC: 0.74–0.85). In the bivariate models, performance in the PZ improved with AUCs >0.90 throughout. Parametric feature maps alone and as bivariate models with PSAD can (?) noninvasively identify csPCa in PI-RADS 3 lesions and could serve as a quantitative tool reducing ambiguity in PI-RADS 3 lesions.

Background:Differentiating inflammatory from malignant lung lesions continues to be challenging in clinical routine, frequently requiring invasive methods like biopsy. Therefore, we aimed to investigate if inflammatory and malignant pulmonary lesions could be distinguished noninvasively using radiomics of apparent diffusion coefficient (ADC) maps and radiomic feature maps calculated from T2-weighted (T2w) 3 Tesla (3T) magnetic resonance imaging (MRI) of the lung.Methods:Fifty-four patients with an unclear pulmonary lesion on computed tomography (CT) were prospectively included and examined by 3T MRI with T2w and diffusion-weighted sequences (b values of 50 and 800). ADC maps were calculated automatically. All patients underwent biopsy or bronchoalveolar lavage (BAL). Sixteen patients were excluded (e.g., motion artifacts), leaving 19 patients each with malignant and inflammatory pulmonary lesions. Target lesions were defined by biopsy or as the largest lesion (BAL-based pathogen detection), and two readers placed volumes of interest (VOIs) around the lesions on T2w images and ADC maps. One hundred and seven features were conventionally extracted from the ADC maps using PyRadiomics. T2w images were converted to 107 parametric feature maps per patient using a PyRadiomics-based, pretested software tool developed by our group. VOIs were copied from T2w images to T2 maps for feature quantification. Features were tested for significant differences using the Mann-Whitney U-test. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis and interreader agreement by intraclass correlation coefficients (ICCs).Results:Fifty-eight features derived from ADC maps differed significantly between malignant and inflammatory pulmonary lesions, with areas under the curve (AUCs) >0.90 for 5 and >0.80 for 27 features, compared with 67 features from T2 maps (5 features with AUCs >0.80). ICCs were excellent throughout.Conclusions:ADC and T2 maps differentiate inflammatory and malignant pulmonary lesions with outstanding (ADC) and excellent (T2w derived feature maps) diagnostic performance. MRI could thus guide the further diagnostic workup and a timely initiation of the appropriate therapy.

In the absence of randomized controlled trials comparing tisagenlecleucel vs. standard of care (SOC) in pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia (r/r ALL), the objective was to compare the efficacy of tisagenlecleucel with historical controls from multiple disease registries using patient-level adjustment of the historical controls. The analysis is based on patient-level data of three tisagenlecleucel studies (ELIANA, ENSIGN and CCTL019B2001X) vs. three registries in Germany/Austria. Statistical analyses were fully pre-specified and propensity score weighting of the historical controls by fine stratification weights was used to adjust for relevant confounders identified by systematic literature review. Results showed high comparability of cohorts after adjustment with absolute SMD ≤ 0.1 for all pre-specified confounders and favorable outcomes for tisagenlecleucel compared to SOC for all examined endpoints. Hazard ratios for OS (Intention to treat)ITT,adjusted , EFS (Full analysis set)FAS,naïve and RFS FAS,naïve were 0.54 (95% CI: 0.41–0.71, p < 0.001), 0.67 (0.52–0.86, p = 0.001) and 0.77 (0.51–1.18, p = 0.233). The OS ITT, adjusted , EFS FAS,naïve and RFS FAS,naive survival probability at 2 years was 59.49% for tisagenlecleucel vs. 36.16% for SOC population, 42.31% vs. 30.23% and 59.60% vs. 54.57%, respectively. Odds ratio for ORR ITT,adjusted was 1.99 (1.33–2.97, p < 0.001). Results for OS and ORR were statistically significant after adjustment for confounders and provide evidence supporting a superiority of tisagenlecleucel in r/r ALL given the good comparability of cohorts after adjustment for confounders.

Different volume of interest (VOI) sizes influence radiomic features. This study examined if translating images into feature maps before feature sampling could compensate for these effects in liver magnetic resonance imaging (MRI). T1- and T2-weighted sequences from three different scanners (two 3-T scanners, one 1.5-T scanner) of 66 patients with normal abdominal MRI were included retrospectively. Three differently sized VOIs (10, 20, and 30 mm in diameter) were drawn in the liver parenchyma (right lobe), excluding adjacent structures. Ninety-three features were extracted conventionally using PyRadiomics. All images were also converted to 93 parametric feature maps using a pretested software. Agreement between the three VOI sizes was assessed with overall concordance correlation coefficients (OCCCs), while OCCCs > 0.85 were rated reproducible. OCCCs were calculated twice: for the VOI sizes of 10, 20, and 30 mm and for those of 20 and 30 mm. When extracted from original images, only 4 out of the 93 features were reproducible across all VOI sizes in T1- and T2-weighted images. When the smallest VOI was excluded, 5 features (T1-weighted) and 7 features (T2-weighted) were reproducible. Extraction from parametric maps increased the number of reproducible features to 9 (T1- and T2-weighted) across all VOIs. Excluding the 10-mm VOI, reproducibility improved to 16 (T1-weighted) and 55 features (T2-weighted). The stability of all other features also increased in feature maps. Translating images into parametric maps before feature extraction improves reproducibility across different VOI sizes in normal liver MRI. The size of the segmented VOI influences the feature quantity of radiomics, while software-based conversion of images into parametric feature maps before feature sampling improves reproducibility across different VOI sizes in MRI of normal liver tissue. • Parametric feature maps can compensate for different VOI sizes. • The effect seems dependent on the VOI sizes and the MRI sequence. • Feature maps can visualize features throughout the entire image stack.

Background Cholecystitis is a rare but dolorous complication after Y90-radioembolization of liver malignancies. Purpose To decide the occlusion of the cystic artery (CA) to prevent cholecystitis after Y90 radioembolization using an algorithm. Material and Methods In 130 patients, the gallbladder was at risk of embolization as the right liver lobe was targeted. Precautionary measures (e.g. coil occlusion of the cystic artery) were decided by enhancement of the gallbladder in pre-treatment Tc99m-MAA SPECT/CT and performed directly before Y90 radioembolization. In non-enhancing cases, the CA was left open. The outcome was determined by clinical symptoms of acute or chronic cholecystitis as well as imaging and laboratory parameters. Findings were additionally classified according to the Tokyo Guidelines of acute cholecystitis. Results Only 16 patients demonstrated enhancement of the gallbladder in Tc99m-MAA SPECT/CT. Including additional indications from angiographic findings, prophylactic measures were scheduled in 22 patients (standard of care). Thus, 121 patients were at risk of non-target embolization to the gallbladder during Y90 microsphere administration (investigative arm). Four cases (3.0%) of cholecystitis occurred by clinical presentation: two patients with onset of acute symptoms within 48 h after Y90 radioembolization (“embolic cholecystitis”) and two patients with late onset of symptoms (“radiogenic cholecystitis”). The incidence of cholecystitis was not significantly more frequent without indication of precautionary measures (investigative cohort 2.9% vs. standard of care 4.7%; P = 0.53). Conclusion The overall incidence of cholecystitis after Y90 radioembolization is low. Determination of cystic artery intervention using Tc99m-MAA SPECT/CT successfully balances the incidence of symptomatic cholecystitis with unnecessary vessel occlusion.

The routine use of dynamic-contrast-enhanced MRI (DCE-MRI) of the liver using hepatocyte-specific contrast agent (HSCA) as the standard of care for the study of focal liver lesions is not widely accepted and opponents invoke the risk of a loss in near 100% specificity of extracellular contrast agents (ECA) and the need for prospective head-to-head comparative studies evaluating the diagnostic performance of both contrast agents. The Purpose of this prospective intraindividual study was to conduct a quantitative and qualitative head-to-head comparison of DCE-MRI using HSCA and ECA in patients with liver cirrhosis and HCC. Twenty-three patients with liver cirrhosis and proven HCC underwent two 3 T-MR examinations, one with ECA (gadoteric acid) and the other with HSCA (gadoxetic acid). Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), wash-in, wash-out, image quality, artifacts, lesion conspicuity, and major imaging features of LI-RADS v2018 were evaluated. Wash-in and wash-out were significantly stronger with ECA compared to HSCA (P < 0.001 and 0.006, respectively). During the late arterial phase (LAP), CNR was significantly lower with ECA (P = 0.005), while SNR did not differ significantly (P = 0.39). In qualitative analysis, ECA produced a better overall image quality during the portal venous phase (PVP) and delayed phase (DP) compared to HSCA (P = 0.041 and 0.008), showed less artifacts in the LAP and PVP (P = 0.003 and 0.034) and a higher lesion conspicuity in the LAP and PVP (P = 0.004 and 0.037). There was no significant difference in overall image quality during the LAP (P = 1), in artifacts and lesion conspicuity during the DP (P = 0.078 and 0.073) or in the frequency of the three major LI-RADS v2018 imaging features. In conclusion, ECA provides superior contrast of HCC—especially hypervascular HCC lesions—in DCE-MR in terms of better perceptibility of early enhancement and a stronger washout.

Purpose: This study aimed to evaluate the diagnostic performance of texture analysis (TA), T1 mapping, and signal intensity quotients derived from fast T1-weighted gradient echo (T1w GRE) sequences for differentiating pulmonary lymphoma manifestations and nonlymphoma infiltrates in possible invasive fungal disease in immunocompromised hematological patients. Materials and Methods: Twenty patients with hematologic malignancies and concomitant immunosuppression (including 10 patients with pulmonary lymphoma manifestations and 10 patients with nonlymphoma infiltrates) prospectively underwent 3 T magnetic resonance imaging using a conventional T1w GRE sequence and a T1w GRE mapping sequence with variable flip angle. A region of interest was placed around the most representative lesion in each patient. TA was performed using PyRadiomics. T1 relaxation times were extracted from precompiled maps and calculated manually. Signal intensity quotients (lesion/muscle) were calculated from conventional T1w GRE sequences. Results: Of all TA features, variance, mean absolute deviation, robust mean absolute deviation, interquartile range, and minimum were significantly different between the 2 entities ( P <0.05), with excellent diagnostic performance in receiver operating characteristic analysis (area under the curve [AUC] >80%). Neither T1 relaxation times from precompiled maps (AUC=63%; P =0.353) nor manual calculation (AUC=63%; P =0.353) nor signal intensity quotients (AUC=70%; P =0.143) yielded significant differences. Conclusions: TA from fast T1w GRE images can differentiate pulmonary lymphoma manifestations and nonlymphoma infiltrates in possible invasive fungal disease with excellent diagnostic performance using the TA features variance, mean absolute deviation, robust mean absolute deviation, interquartile range, and minimum. Combining a fast T1w GRE sequence with TA seems to be a promising tool to differentiate these 2 entities noninvasively.

The value of gadoxetic acid in the diagnosis of hepatocellular carcinoma (HCC), based on perfusion criteria, is under dispute. This post-hoc analysis of the prospective, phase II, randomized, controlled SORAMIC study compared the accuracy of gadoxetic acid-enhanced dynamic magnetic resonance imaging (MRI) (arterial, portovenous, and venous phase only) versus contrast-enhanced computed tomography (CT) for stratifying patients with HCC to curative ablation or palliative treatment. Two reader groups (radiologists, R1 and R2) performed blind reads of CT and gadoxetic acid-enhanced MRI (contrast dynamics only). A truth panel, with access to clinical and imaging follow-up data, served as reference. Primary endpoint was non-inferiority (margin: 5% points) of MRI vs. CT (lower 95% confidence interval [CI] > 0.75) in a first step and superiority (complete 95% CI > 1) in a second step. The intent-to-treat population comprised 538 patients. Accuracy of treatment decisions was 73.4% and 70.8% for CT (R1 and R2, respectively) and 75.1% and 70.3% for gadoxetic acid-enhanced dynamic MRI. Non-inferiority but not superiority of gadoxetic acid-enhanced dynamic MRI versus CT was demonstrated (odds ratio 1.01; CI 0.97–1.05). Despite a theoretical disadvantage in wash-out depiction, gadoxetic acid-enhanced dynamic MRI is non-inferior to CT in accuracy of treatment decisions for curative ablation versus palliative strategies. This outcome was not subject to the use of additional MR standard sequences.

18F-FDG-PET/CT is standard to assess response in Hodgkin lymphoma by quantifying metabolic activity with the Deauville score. PET/CT, however, is time-consuming, cost-extensive, linked to high radiation and has a low availability. As an alternative, we investigated radiomics from non-contrast-enhanced computed tomography (NECT) scans. 75 PET/CT examinations of 43 patients on two different scanners were included. Target lesions were classified as Deauville score 4 positive (DS4+) or negative (DS4-) based on their SUVpeak and then segmented in NECT images. From these segmentations, 107 features were extracted with PyRadiomics. All further statistical analyses were then performed scanner-wise: differences between DS4+ and DS4- manifestations were assessed with the Mann-Whitney-U-test and single feature performances with the ROC-analysis. To further verify the reliability of the results, the number of features was reduced using different techniques. The feature median showed a high sensitivity for DS4+ manifestations on both scanners (scanner A: 0.91, scanner B: 0.85). It furthermore was the only feature that remained in both datasets after applying different feature reduction techniques. The feature median from NECT concordantly has a high sensitivity for DS4+ Hodgkin manifestations on two different scanners and thus could provide a surrogate for increased metabolic activity in PET/CT.

Purpose The aim of this study was to evaluate brain FDG PET for short- to medium-term prediction of cognitive decline, need for assisted living, and survival in acutely hospitalized geriatric patients with newly detected clinically uncertain cognitive impairment (CUCI). Materials and Methods The study included 96 patients (62 females, 81.4 ± 5.4 years) hospitalized due to (sub)acute admission indications with newly detected CUCI (German Clinical Trials Register DRKS00005041). FDG PET was categorized as “neurodegenerative” (DEG+) or “nonneurodegenerative” (DEG−) based on visual inspection by 2 independent readers. In addition, each individual PET was tested voxel-wise against healthy controls (P < 0.001 uncorrected). The resulting total hypometabolic volume (THV) served as reader-independent measure of the spatial extent of neuronal dysfunction/degeneration. FDG PET findings at baseline were tested for association with the change in living situation and change in vital status 12 to 24 months after PET. The association with the annual change of the CDR-SB (Clinical Dementia Rating Sum of Boxes) after PET was tested in a subsample of 72 patients. Results The mean time between PET and follow-up did not differ between DEG+ and DEG− patients (1.37 ± 0.27 vs 1.41 ± 0.27 years, P = 0.539). Annual change of CDR-SB was higher in DEG+ compared with DEG− patients (2.78 ± 2.44 vs 0.99 ± 1.81, P = 0.001), and it was positively correlated with THV (age-corrected Spearman ρ = 0.392, P = 0.001). DEG+ patients moved from at home to assisted living significantly earlier than DEG− patients (P = 0.050). Survival was not associated with DEG status or with THV. Conclusions In acutely hospitalized geriatric patients with newly detected CUCI, the brain FDG PET can contribute to the prediction of further cognitive/functional decline and the need for assisted living within 1 to 2 years.

BACKGROUND:In radiomics studies, differences in the volume of interest (VOI) are often inevitable and may confound the extracted features. We aimed to correct this confounding effect of VOI variability by applying parametric maps with a fixed voxel size.METHODS:Ten scans of a cup filled with sodium chloride solution were scanned using a multislice computed tomography (CT) unit. Sphere-shaped VOIs with different diameters (4, 8, or 16 mm) were drawn centrally into the phantom. A total of 93 features were extracted conventionally from the original images using PyRadiomics. Using a self-designed and pretested software tool, parametric maps for the same 93 features with a fixed voxel size of 4 mm3 were created. To retrieve the feature values from the maps, VOIs were copied from the original images to preserve the position. Differences in feature quantities between the VOI sizes were tested with the Mann-Whitney U-test and agreement with overall concordance correlation coefficients (OCCC).RESULTS:Fifty-five conventionally extracted features were significantly different between the VOI sizes, and none of the features showed excellent agreement in terms of OCCCs. When read from the parametric maps, only 8 features showed significant differences, and 3 features showed an excellent OCCC (≥ 0.85). The OCCCs for 89 features substantially increased using the parametric maps.CONCLUSIONS:This phantom study shows that converting CT images into parametric maps resolves the confounding effect of VOI variability and increases feature reproducibility across VOI sizes.

Background: Around 15% of children with acute lymphoblastic leukemia (ALL) experience disease relapse. The prognosis of these patients largely depends on the site of recurrence, time to relapse and leukemia immunophenotype. The ALL-REZ BFM 2002 and the ALL R3 trials have proved to be effective in previous trials. The IntReALL SR 2010 trial, conducted under the umbrella of the I-BFM SG, aimed at investigating feasibility, toxicity and efficacy of both treatment strategies in a large multi-national, multi-center prospective randomized trial. Methods: Patients with a first standard-risk (SR) ALL relapse aged 1 - 17 years were recruited to the trial from 23/Oct/2014 to 31/Jul/2020 in 17 countries (210 centers). SR relapse criteria were: late (≥ 6 months after end of initial therapy) isolated bone marrow (BM) relapse, late or early (< 6 months after end of initial therapy and ≥ 18 months after initial diagnosis) combined BCP-ALL BM relapse, any late/early isolated extramedullary (IEM) relapse. They were randomized at a 1:1 rate to receive either arm A (ALL-REZ BFM 2002) or B (ALL R3). During consolidation, patients were randomized to receive the CD22-directed monoclonal antibody epratuzumab in addition to backbone chemotherapy. Results of this 2nd randomization will be communicated separately. Patients with late BM relapse were allocated to consolidation and maintenance chemotherapy or to allogeneic hematopoietic stem-cell transplantation (HSCT), depending on their minimal residual disease (MRD, cut-off arm A 10e-3 and arm B 10e-4) assessed after induction therapy. Patients with early either combined BM or IEM relapse were allocated to receive allogeneic HSCT. Results: Overall, 620 patients were randomized to receive arm A (n=304) or Arm B (n=316). Patient's characteristics were equally distributed among both groups (table 1). Induction death, 2nd remission rate, death in remission (5-years cumulative incidence (CI) 4.1 vs 7.4%, p=0.10), and subsequent relapse rates by arm A and B (CI 23.8 vs 22.8, p=0.80) did not differ between both groups. The MRD response rate with < 10e-4 post induction was significantly higher in Arm B (p=0.015), but not significantly different based on the arm specific cut-off, leading to comparable rates of allogeneic HSCT. The probability of 5-years event-free survival (pEFS) with arm A versus arm B was 70.2±3.1 SE versus 68.5±3.1 (p=0.61, figure 1) and that of overall survival (pOS) was 86.7±2.3 versus 87.1±2.0 (p=0.8). Subgroup analyses revealed a significantly higher pEFS in patients with isolated CNS relapse when treated with arm A (81.6±6.3, n=40) compared to arm B (43.3±8.3, n=45, p=0.001), whereas in patients with BM involvement or those with non-CNS IEM relapse, no significant difference was found (p=0.41). However, patients with isolated BM relapse experienced a higher CI of subsequent relapse with arm A (12.5±2.1, n=146) as compared to arm B (6.5±1.6, n=153, p=0.008). Patients with late BM relapse and MRD poor response after induction had comparable pDFS (arm A 65.8±6.4, n=74; arm B 68.8±6.2, n=75; p=0.71), which also did not differ from that of patients with MRD good response (arm A 67.7±5.6, n=100; arm B 68.9±5.6, n=113; p=0.77). Patients with late IEM relapse achieved a pEFS of 86.7±4.6 whereas those with early relapse and HSCT indication achieved a pEFS 61.8±5.4 (p=0.0004). Rates of reported severe adverse events (SAEs) per treatment phase did not differ between arms except nervous system disorders occurring more frequently in arm A (p=0.03, table 1). Conclusion: Both arm A and B were effective in this large multi-national trial. EFS and OS probabilities compare favorably to results recently published by other cooperative groups. In particular, the outcome of patients with early IEM relapse or with late BM relapse and MRD poor response is encouraging confirming the benefit of allo HSCT in these subgroups. Due to superior outcome of isolated CNS relapse with arm A, patients without BM involvement will receive that arm as backbone in future trials. Since arm B showed a better MRD response rate after induction and a lower relapse rate in patients with BM relapse, it will be implemented as backbone for future trials in patients with BM involvement. Toxicity (TRM and SAE rates) is substantial in both arms demonstrating the urgent medical need of replacing toxic chemotherapy elements with equally effective, but less toxic targeted immunotherapy strategies in future trials. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Background: To investigate whole-body contrast-enhanced CT and hepatobiliary contrast liver MRI for the detection of extrahepatic disease (EHD) in hepatocellular carcinoma (HCC) and to quantify the impact of EHD on therapy decision. Methods: In this post-hoc analysis of the prospective phase II open-label, multicenter, randomized controlled SORAMIC trial, two blinded readers independently analyzed the whole-body contrast-enhanced CT and gadoxetic acid-enhanced liver MRI data sets of 538 HCC patients. EHD (defined as tumor manifestation outside the liver) detection rates of the two imaging modalities were compared using multiparametric statistical tests. In addition, the most appropriate treatment recommendation was determined by a truth panel. Results: EHD was detected significantly more frequently in patients with portal vein infiltration (21% vs. 10%, p < 0.001), macrovascular infiltration (22% vs. 9%, p < 0.001), and bilobar liver involvement (18% vs. 9%, p = 0.006). Further on, the maximum lesion diameter in patients with EHD was significantly higher (8.2 cm vs. 5.8 cm, p = 0.002). CT detected EHD in significantly more patients compared to MRI in both reader groups (p < 0.001). Higher detection rates of EHD in CT led to a change in management only in one patient since EHD was predominantly present in patients with locally advanced HCC, in whom palliative treatment is the standard of care. Conclusions: Whole-body contrast-enhanced CT shows significantly higher EHD detection rates compared to hepatobiliary contrast liver MRI. However, the higher detection rate did not yield a significant impact on patient management in advanced HCC.

Abstract Introduction: Acute lymphoblastic leukemia (ALL) is the most common cancer affecting children and its cure rates are close to 90%. Nevertheless, relapsed ALL is still a major cause of cancer-associated deaths in children. Therefore, the multicenter trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002 was designed to improve the prognosis of children with relapsed ALL by introducing new chemotherapy elements. Little is known though about the prognostic relevance of deviations from the ALL protocols. This study aimed to investigate the characteristics of such protocol deviations and to determine their prognostic relevance for the relapsed disease. Methods: We performed a retrospective analysis of 686 children and adolescents up to 18 years of age with first relapse of ALL who were enrolled between 2002 and 2012 in the ALL-REZ BFM 2002 Study. Deviations were identified in terms of time and type. In order to investigate the prognostic importance of the time delay, the 90th percentile of delays between defined treatment elements (i.e. 15.5 days) was used as a cut-off point. Furthermore, deviations were categorized as avoidable (logistics, family/PI decisions) and non-avoidable (clear medical indication). The protocol deviation occurred during the course of therapy was therefore considered as a time-dependent variable. Disease-free survival, (DFS, induction failures excluded) and OS were analyzed using Kaplan-Meier estimate, log-rank test, Mantel-Byar test and Cox/logistic regression (univariate and multivariate analyses). Results: A total of 587 patients (86%) received the protocol therapy, whereas 99 patients (14%) underwent deviations during their treatment. Baseline characteristics were compared in both groups (Table 1). Deviations were categorized as: change of chemotherapy in 48% of the patients (n=47/99), stop of chemotherapy in 10 % (n=10/99), non-protocol compliant reaction to MRD findings in 28% (n=28/99) and change of radiation treatment in 14% (n=14/99). The cumulative incidence of protocol deviation was 6% and 15.5% at 3 and 9 months, respectively (Figure 1). The remission rate of patients with protocol deviation during induction was slightly lower compared to patients without such deviation (24/29, 83% vs. 579/657, 88%; P=0.38). The estimated 5-year probabilities of DFS and OS between the patients treated according to protocol therapy and those with deviations were significantly different (pDFS, Protocol therapy: 0.61 ± 0.02 vs. Deviation: 0.38 ± 0.05, P < 0.001; pOS, Protocol: 0.70 ± 0.02 vs. Deviation: 0.57 ± 0.05, P < 0.001; Figure 2, 3). In multivariate analyses protocol deviation, time point of relapse and immunophenotype turned out to be independent prognostic factors of the DFS (Table2). The hazard ratio of the protocol deviation was significant only in patients with the late relapse, whereas in patients with early/very early relapse no significant prognostic effect could be found [late (n=40): HR=2.53, 95%CI 1.53-4.21, P<0.001; early (n=29): HR=1.49, 95%CI 0.88-2.51, P=0.13; very early (n=25): HR=1.50, 95%CI 0.84-2.66, P=0.17]. Moreover, DFS probabilities were comparable for avoidable (n=63) and non-avoidable (n=31) deviations (0.43 ± 0.07 vs. 0.40 ± 0.09, P=0.9; Non avoidable: HR=1.19, 95%CI=0.68-2.10, P= 0.53). In terms of the time-related deviations, the extent of the delays between induction and beginning of consolidation therapy was not significantly associated with the DFS [≤90th percentile (n=319/603); pDFS: =0.60 ± 0.02 vs. >90th percentile (n=36/603); pDFS: 0.56 ± 0.08, P=0.3]. Treatment delays during other phases of the protocol were also not related to the outcome. Conclusion: While protocol deviations did not significantly affect remission rates in this study, they were significantly related to inferior DFS. Since a relevant part of the protocol deviations could be classified as avoidable, strict protocol compliance should lead to improved outcomes. The prognostic impact of protocol deviations was in particular relevant in patients with late relapse with generally rather chemosensitive diseases and better prognosis. In this analysis, treatment delays did not influence the outcome. Figure 1 Figure 1. Disclosures von Stackelberg: Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Miltenyi: Consultancy, Honoraria.