Real-world response assessment of immune checkpoint inhibition: comparing iRECIST and RECIST 1.1 in melanoma and non-small cell lung cancer patients.

OBJECTIVES: To compare immune response evaluation criteria in solid tumors (iRECIST) and response evaluation criteria in solid tumors (RECIST) 1.1 for response assessment of immune checkpoint inhibitor (ICI) therapy in a real-world setting in patients with melanoma and non-small cell lung cancer (NSCLC). METHODS: Two-hundred fifty-two patients with melanoma and NSCLC who received CTLA-4 inhibitor ipilimumab or PD-1 inhibitors nivolumab or pembrolizumab and who underwent staging CT of the chest and abdomen were retrospectively included. Treatment response evaluation according to the RECIST 1.1 and iRECIST guidelines was performed for all patients. Response patterns, as well as overall response rate (ORR), disease control rate (DCR), and time to progression (TTP), were compared between RECIST 1.1 and iRECIST. RESULTS: Out of 143 patients with progressive disease (PD) according to RECIST 1.1, 48 (33.6%) did not attain confirmation of progression (iCPD) as per iRECIST and six patients who were treated beyond RECIST 1.1 progression reached PD at a later point in time in iRECIST, resulting in a significant difference in TTP between iRECIST and RECIST 1.1 (618.3 ± 626.9 days vs. 538.1 ± 617.9 days, respectively (p < 0.05)). The number of non-responders as per RECIST 1.1 was 79, whereas it was 60 when using iRECIST. ORR was 28.5% for RECIST 1.1 and 34.1% for iRECIST, and corresponding DCR of 67.4% for RECIST 1.1 and 74.6% for iRECIST. CONCLUSION: iRECIST was more suitable than RECIST 1.1 for capturing atypical response patterns to ICI therapy in patients with melanoma and NSCLC, resulting in differences in the assessment of treatment response. CLINICAL RELEVANCE STATEMENT: Compared to RECIST 1.1, iRECIST may improve patient care and treatment decisions for patients with NSCLC or melanoma who are treated with immune checkpoint inhibitors in clinical routine. KEY POINTS: RECIST 1.1 may incorrectly assess atypical treatment patterns to immune checkpoint inhibitors. iRECIST better captured atypical response patterns compared to RECIST 1.1. iRECIST was more suitable for assessing response to immune checkpoint inhibitors in non-small cell lung carcinoma and melanoma.

Deep-Learning-Based Image Denoising in Imaging of Urolithiasis: Assessment of Image Quality and Comparison to State-of-the-Art Iterative Reconstructions.

This study aimed to compare the image quality and diagnostic accuracy of deep-learning-based image denoising reconstructions (DLIDs) to established iterative reconstructed algorithms in low-dose computed tomography (LDCT) of patients with suspected urolithiasis. LDCTs (CTDIvol, 2 mGy) of 76 patients (age: 40.3 ± 5.2 years, M/W: 51/25) with suspected urolithiasis were retrospectively included. Filtered-back projection (FBP), hybrid iterative and model-based iterative reconstruction (HIR/MBIR, respectively) were reconstructed. FBP images were processed using a Food and Drug Administration (FDA)-approved DLID. ROIs were placed in renal parenchyma, fat, muscle and urinary bladder. Signal- and contrast-to-noise ratios (SNR/CNR, respectively) were calculated. Two radiologists evaluated image quality on five-point Likert scales and urinary stones. The results showed a progressive decrease in image noise from FBP, HIR and DLID to MBIR with significant differences between each method (p < 0.05). SNR and CNR were comparable between MBIR and DLID, while it was significantly lower in HIR followed by FBP (e.g., SNR: 1.5 ± 0.3; 1.4 ± 0.4; 1.0 ± 0.3; 0.7 ± 0.2, p < 0.05). Subjective analysis confirmed best image quality in MBIR, followed by DLID and HIR, both being superior to FBP (p < 0.05). Diagnostic accuracy for urinary stone detection was best using MBIR (0.94), lowest using FBP (0.84) and comparable between DLID (0.90) and HIR (0.90). Stone size measurements were consistent between all reconstructions and showed excellent correlation (r2 = 0.958-0.975). In conclusion, MBIR yielded the highest image quality and diagnostic accuracy, with DLID producing better results than HIR and FBP in image quality and matching HIR in diagnostic precision.

Association between pouch morphology, cardiovascular risk factors and ischemic brain lesions in patients with left-sided septal pouches.

BACKGROUND: Left atrial outpouching structures such as left atrial diverticula (LADs) and left-sided septal pouches (LSSPs) might be a source of cryptogenic stroke. This imaging study evaluates the association between pouch morphology, patient comorbidities and ischemic brain lesions (IBLs). METHODS: This is a retrospective single-center analysis of 195 patients who received both a cardiac CT and a cerebral MRI. LADs, LSSPs, and IBLs were retrospectively identified. Size measurements included pouch width, length and volume for LADs and circumference, area and volume for LSSPs. The association between LADs/LSSPs, IBLs and cardiovascular comorbidities was determined by univariate and bivariate regression analyses. RESULTS: The prevalence and mean volume were 36.4% and 372 ± 569 mm3 for LSSPs, and 40.5% and 415 ± 541 mm3 for LADs. The IBL prevalence was 67.6% in the LSSP group and 48.1% in the LAD group. LSSPs had 2.9-fold increased hazards of IBLs (95%CI: 1.2-7.4, p = 0.024), and LADs showed no significant correlation with IBLs. Size measurements had no impact on IBLs. A co-existing LSSP was associated with an increased prevalence of IBLs in patients with coronary artery disease (HR: 1.5, 95%CI: 1.1-1.9, p = 0.048), heart failure (HR: 3.7, 95%CI: 1.1-14.6, p = 0.032), arterial hypertension (HR: 1.9, 95%CI: 1.1-3.3, p = 0.017), and hyperlipidemia (HR: 2.2, 95%CI: 1.1-4.4, p = 0.018). CONCLUSION: Co-existing LSSPs were associated with IBLs in patients with cardiovascular risk factors, however, pouch morphology did not correlate with the IBL rate. Upon confirmation by further studies, these findings might be considered in the treatment, risk stratification, and stroke prophylaxis of these patients.

Virtual non-contrast reconstructions improve differentiation between vascular enhancement and calcifications in stereotactic planning CT scans of cystic intracranial tumors.

PURPOSE: To assess the diagnostic value of spectral-detector CT (SDCT) derived virtual non-contrast images (VNC) for differentiation between vascular enhancement and wall calcifications of cystic intracranial tumors in contrast-enhanced stereotactic planning examinations. METHOD: 48 patients with cystic intracranial tumors who underwent stereotactic SDCT examinations between 02/2017 and 02/2020 were retrospectively included. In each patient, two separate hyperattenuating structures along the cyst wall were defined as either enhancement or calcification, respectively, using reference MRI examinations. Quantitative analysis was performed ROI-based in conventional images (CI) and VNC. In the subjective analysis, two radiologists diagnosed the predefined peri-cystic structures in binary decisions as either enhancement or calcification using CI and the combination of CI and VNC, and rated diagnostic confidence, image noise and removal of iodine in VNC. Moreover, a potential diagnostic benefit of VNC was indicated. RESULTS: Attenuation in CI was higher as compared to VNC across all assessed ROI (all p < 0.01). In VNC, CNR between calcification and white matter was significantly higher as compared to CNR between vascular enhancement and white matter (2.6 vs 1.3, p < 0.01), while there was no significant difference in CI. In the qualitative assessment, diagnostic accuracy was significantly higher using both VNC and CI compared to using CI alone. Raters reported less image noise in VNC as compared to CI. An additional diagnostic benefit of VNC was indicated in 84.4 % of all cases. CONCLUSIONS: SDCT-derived VNC images facilitate differentiation between peri-cystic contrast enhancement in blood vessels and calcifications in stereotactic planning scans of cystic intracranial tumors.

The Aortic Ductus Diverticulum-Innocent Bystander or Potential Source of Thromboembolic Stroke?

OBJECTIVE: Due to reversal blood flow in the diastolic phase, outpouchings at the aortic isthmus may carry the risk of thrombus formation and subsequent thromboembolism. The objective was to evaluate the association between aortic ductus diverticula (ADDs) and ischemic brain alterations in cerebral magnetic resonance imaging. METHODS: A retrospective analysis of 218 patients who received both a dedicated computed tomography angiography of the thoracic aorta and a brain magnetic resonance imaging was performed. Two radiologists independently reviewed all examinations for the presence of ADD as well as ischemic alterations of the brain. The association between this anatomical variant and ischemic brain alterations was evaluated by univariate and bivariate logistic regression analyses. RESULTS: ADDs were identified/present in 35 of 218 patients (16%). Ischemic brain alterations were found in 57% of patients (20/35) with an ADD and in 42% of the control group (77/183, P = 0.1). The presence of an ADD did not prove to be an independent risk factor for ischemic brain alterations after multivariate adjustment (odds ratio = 1.7, 95% confidence interval = 0.72-3.96, P = 0.225). CONCLUSIONS: In the present study, ADDs were not significantly associated with ischemic brain alterations. Therefore, ADDs seem to be an innocent bystander with respect to the pathogenesis of ischemic brain alterations.

Quantitative determination of pulmonary emphysema in follow-up LD-CTs of patients with COVID-19 infection.

PURPOSE: To evaluate the association between the coronavirus disease 2019 (COVID-19) and post-inflammatory emphysematous lung alterations on follow-up low-dose CT scans. METHODS: Consecutive patients with proven COVID-19 infection and a follow-up CT were retrospectively reviewed. The severity of pulmonary involvement was classified as mild, moderate and severe. Total lung volume, emphysema volume and the ratio of emphysema/-to-lung volume were quantified semi-automatically and compared inter-individually between initial and follow-up CT and to a control group of healthy, age- and sex-matched patients. Lung density was further assessed by drawing circular regions of interest (ROIs) into non-affected regions of the upper lobes. RESULTS: A total of 32 individuals (mean age: 64 ± 13 years, 12 females) with at least one follow-up CT (mean: 52 ± 66 days, range: 5-259) were included. In the overall cohort, total lung volume, emphysema volume and the ratio of lung-to-emphysema volume did not differ significantly between the initial and follow-up scans. In the subgroup of COVID-19 patients with > 30 days of follow-up, the emphysema volume was significantly larger as compared to the subgroup with a follow-up < 30 days (p = 0.045). Manually measured single ROIs generally yielded lower attenuation values prior to COVID-19 pneumonia, but the difference was not significant between groups (all p > 0.05). CONCLUSION: COVID-19 patients with a follow-up CT >30 days showed significant emphysematous lung alterations. These findings may help to explain the long-term effect of COVID-19 on pulmonary function and warrant validation by further studies.

Structural differences in impaired verbal fluency in essential tremor patients compared to healthy controls.

OBJECTIVE: We wanted to identify differences in grey and white matter in essential tremor patients compared to controls in the non-motor domain, using the example of impaired verbal fluency. BACKGROUND: A disturbance of verbal fluency in essential tremor patients compared to healthy controls is behaviorally well described. METHODS: Voxel-based morphometry and tract-based spatial statistics were used to analyze structural differences in grey and white matter in 19 essential tremor patients compared to 23 age- and gender-matched controls. RESULTS: Several significant observations were made. (I) There was less grey matter in the predominantly right precuneus in the essential tremor group compared to controls [p < .001]. (II) In ET patients mean, axial, and radial diffusivity values broadly correlated with the tremor rating scale, pronounced in fronto-parietal regions [p < .05]. (III) In ET patients there was a significant decline in fractional anisotropy values in the corpus callosum in the correlation with verbal fluency results [p < .05]; by inclusion of the tremor rating scale as covariate of no interest this significance was however diminished to a tendency (p < .1). No significant results were found in these within-group correlations in grey matter analyses for ET patients (p > .05). CONCLUSION: The present results indicate that non-motor symptoms such as verbal fluency (VBF) in ET have a structural substrate; their reproduction requires the integration of potential environmental plasticity effects, differentiation into individual clinical subtypes and a careful handling with methodological peculiarities of structural MR imaging.

The differentiated networks related to essential tremor onset and its amplitude modulation after alcohol intake.

The dysregulation of endogenous rhythms within brain networks have been implicated in a broad range of motor and non-motor pathologies. Essential tremor (ET), classically the purview of a single aberrant pacemaker, has recently become associated with network-level dysfunction across multiple brain regions. Specifically, it has been suggested that motor cortex constitutes an important node in a tremor-generating network involving the cerebellum. Yet the mechanisms by which these regions relate to tremor remain a matter of considerable debate. We sought to discriminate the contributions of cerebral and cerebellar dysregulation by combining high-density electroencephalography with subject-specific structural MRI. For that, we contrasted ET with voluntary (mimicked) tremor before and after ingestion of alcohol to regulate the tremorgenic networks. Our results demonstrate distinct loci of cortical tremor coherence, most pronounced over the sensorimotor cortices in healthy controls, but more frontal motor areas in ET-patients consistent with a heightened involvement of the supplementary motor area. We further demonstrate that the reduction in tremor amplitude associated with alcohol intake is reflected in altered cerebellar - but not cerebral - coupling with movement. Taken together, these findings implicate tremor emergence as principally associated with increases in activity within frontal motor regions, whereas modulation of the amplitude of established tremor relates to changes in cerebellar activity. These findings progress a mechanistic understanding of ET and implicate network-level vulnerabilities in the rhythmic nature of communication throughout the brain.

Time reproduction deficits in essential tremor patients.

BACKGROUND: Although motor symptoms predominate in essential tremor, increasing evidence indicates additional cognitive deficits. According to the pivotal role of cognitive functioning for temporal information processing and acknowledging the relevance of temporal information processing for movement coordination, we investigated whether essential tremor patients exhibit time reproduction deficits. METHODS: A total of 24 essential tremor patients and 24 healthy controls performed sub- and suprasecond visual duration reproduction tasks of 500 to 900 milliseconds and 1.6 to 2.4 seconds, respectively. To differentiate deficient time processing from motor or other cognitive dysfunctions, the average temporal reproduction errors were correlated with tremor severity, immediate and delayed word-list recall performance, and verbal fluency. RESULTS: Essential tremor patients significantly underreproduced sub- and suprasecond time intervals longer than 800 milliseconds. Moreover, time compression correlated significantly with semantic verbal fluency and word-list retrieval performance, but not with tremor severity. CONCLUSION: Data suggest impaired temporal processing in essential tremor, corroborating evidence for specific cognitive deficits. © 2016 International Parkinson and Movement Disorder Society.