Improved Detection of Foreign Bodies on Radiographs Using X-ray Dark-Field and Phase-Contrast Imaging

Purpose: The aim of this study was to investigate whether the detection of foreign bodies can be improved using dark-field and phase-contrast radiography compared with conventional (transmission) radiographs. Materials and Methods: Experiments were performed using ex vivo pig paws, which were prepared with differently sized foreign bodies of metal, wood, and glass (n = 10 each). Paws without foreign bodies served as controls (n = 30). All images were acquired using an experimental grating-based large object radiography system. Five blinded readers (second- to fourth-year radiology residents) were asked to assess the presence or absence of any foreign body. Sensitivity and specificity for the detection of metal, wood, glass, and any foreign body were calculated and compared using McNemar test and generalized linear mixed models. Results: Sensitivity for the detection of metal foreign bodies was 100% for all readers and image combinations. The sensitivity for the detection of wooden foreign bodies increased from 2% for transmission images to 78% when dark-field images were added (P < 0.0001). For glass foreign bodies, sensitivity increased from 84% for transmission images to 96% when adding phase-contrast images (P = 0.041). Sensitivity for the detection of any foreign body was 91% when transmission, dark-field, and phase-contrast images were viewed simultaneously, compared with 62% for transmission images alone (P < 0.0001). Specificity was 99% to 100% across all readers and radiography modalities. Conclusions: Adding dark-field images substantially improves the detection of wooden foreign bodies compared with the analysis of conventional (transmission) radiographs alone. Detection of glass foreign bodies was moderately improved when adding phase-contrast images

Retinal axonal degeneration in Niemann–Pick type C disease

Objective Niemann–Pick disease type C1 (NPC1) is a rare autosomal-recessive lysosomal storage disorder presenting with a broad clinical spectrum ranging from a severe infantile-onset neurovisceral disorder to late-onset neurodegenerative disease. Optical coherence tomography (OCT) is established to detect retinal degeneration in vivo. We examined NPC1-patients (NPC1-P), clinically asymptomatic NPC1-mutation carriers (NPC1-MC), and healthy controls (HC) to (1) identify retinal degeneration in NPC1-disease and (2) to investigate possible subclinical retinal degeneration in NPC1-MC. Methods Fourteen NPC1-P, 17 NPC1-MC, and 31 age-matched HC were examined using spectral-domain OCT. Neurological examinations, clinical scales [modified Disability Rating Scale (mDRS); Scale for the Rating and Assessment of Ataxia (SARA); Spinocerebellar Ataxia Functional Index (SCAFI)], and video-oculography (VOG) were correlated with OCT data. Results Macular retinal nerve fiber layer and volumes of combined ganglion cell and inner plexiform layer were significantly lower in NPC1-P compared to HC [mRNFL (µm):0.13 ± 0.01 vs. 0.14 ± 0.02; p = 0.01; GCIPL (mm3):0.60 ± 0.05 vs. 0.62 ± 0.04; p = 0.04]. No significant differences were found in NPC1-MC in comparison to HC. In NPC1-P, the amplitude of upward vertical saccades showed positive associations with peripapillary RNFL (ρ = 0.645; p < 0.05), and thinned GCIP (ρ = 0.609; p < 0.05), but not in NPC1-MC. In NPC1-P correlations between combined outer plexiform layer and outer nuclear layer (OPONL) with mDRS (r = − 0.617; p < 0.05) and GCIP with SARA (r = − 0.622; p < 0.05) were observed. Furthermore, in NPC1-MC, motor scores were negatively associated with pRNFL (ρ = − 0.677; p < 0.01). Conclusions Using OCT, we showed retinal degeneration in NPC1-P and significant correlation between retinal neuroaxonal degeneration with clinical measurements. We observed a non-significant trend of retinal degeneration in NPC1-MC correlating with subclinical motor abnormalities. Based on these preliminary data, OCT may be an important marker of neurodegeneration in NPC1-disease after onset of clinical symptoms

Early monocyte response following local ablation in hepatocellular carcinoma

Local ablative therapies are established treatment modalities in the treatment of early- and intermediate-stage hepatocellular carcinoma (HCC). Systemic effects of local ablation on circulating immune cells may contribute to patients’ response. Depending on their activation, myeloid cells are able to trigger HCC progression as well as to support anti-tumor immunity. Certain priming of monocytes may already occur while still in the circulation. By using flow cytometry, we analyzed peripheral blood monocyte cell populations from a prospective clinical trial cohort of 21 HCC patients following interstitial brachytherapy (IBT) or radiofrequency ablation (RFA) and investigated alterations in the composition of monocyte subpopulations and monocytic myeloid-derived suppressor cells (mMDSCs) as well as receptors involved in orchestrating monocyte function. We discovered that mMDSC levels increased following both IBT and RFA in virtually all patients. Furthermore, we identified varying alterations in the level of monocyte subpopulations following radiation compared to RFA. (A) Liquid biopsy liquid biopsy of circulating monocytes in the future may provide information on the inflammatory response towards local ablation as part of an orchestrated immune response

The value of sorafenib trough levels in patients with advanced hepatocellular carcinoma - a substudy of the SORAMIC trial.

Background: Sorafenib for advanced hepatocellular carcinoma (HCC) is dose adjusted by toxicity. Preliminary studies have suggested an association between plasma concentrations of sorafenib and its main metabolite (M2) and clinical outcomes. This study aimed to validate these findings and establish target values for sorafenib trough concentrations.Methods: Patients with advanced HCC were prospectively recruited within a multicenter phase II study (SORAMIC). Patients with blood samples available at trough level were included for this pharmacokinetic (PK) substudy. Trough plasma concentrations of sorafenib and its main metabolite (M2) were associated with sorafenib-related toxicity and overall survival (OS).Results: Seventy-four patients were included with a median OS of 19.7 months (95% CI 16.1-23.3). Patients received sorafenib for a median of 51 weeks (IQR 27-62) and blood samples were drawn after a median of 25 weeks (IQR 10-42). Patients had a median trough concentration of 3217 ng/ml (IQR 2166-4526) and 360 ng/ml (IQR 190-593) with coefficients of variation of 65% and 146% for sorafenib and M2, respectively. Patients who experienced severe sorafenib-related toxicity received a lower average daily dose (551 vs 730 mg/day, p = .003), but showed no significant differences in sorafenib (3298 vs 2915 ng/ml, p = .442) or M2 trough levels (428 vs 283 ng/ml, p = .159). Trough levels of sorafenib or M2 showed no significant association with OS.Conclusions: In patients with advanced HCC treated with sorafenib, the administered dose, trough levels of sorafenib or M2, and clinical outcomes were poorly correlated. Toxicity-adjusted dosing remains the standard for sorafenib treatment

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

Dynamics in Circulating y -55Proinflammatory Biomarkers for Prognostic Assessment of Patients With Advanced HCC – A Substudy From the SORAMIC Trial

Introduction: Prediction of response to treatment in patients with advanced hepatocellular carcinoma (HCC) may assist in the selection of personalized management. Objective: This exploratory analysis of the palliative arm of the SORAMIC trial (ClinicalTrials.gov NCT01126645) evaluated the prognostic potential of basal and dynamic changes in systemic levels of interleukin 6 (IL-6), interleukin 8 (IL-8), systemic vascular endothelial growth factor (VEGF), and lipopolysaccharide (LPS). Methods: We evaluated the correlations between overall survival (OS) and concentrations of IL-6, IL-8, VEGF, and LPS at follow-up approximately 7-9 weeks after treatment initialization (FU) compared to baseline (BL) in 90 patients treated either with 90Yttrium (90Y) microspheres combined with sorafenib (n = 44) or with sorafenib (n = 46) alone. Results: Changes in IL-6 concentration during treatment showed correlations with the outcome. An increase in IL-6 concentration of less than 16.8 pg/mL over baseline readings was associated with better survival [median OS 16.3 months compared with 8.9 months (p = 0.0354)]. Correlations with survival were not observed for VEGF or LPS concentrations at baseline, at FU, or changes between these time points. Conclusions: Changes in IL 6 serum levels at 7-9 weeks after treatment initialization but not in IL 8, VEGF, or LPS add important information on the outcome of advanced HCC patients treated palliatively within the SORAMIC trial

Evaluation of MRI in the diagnostic accuracy of extrahepatic metastases in neuroendocrine tumors in comparison with the reference standard somatostatin-receptor–PET/CT

PurposeThe aim of this study was to compare the diagnostic performance of different sets of MR sequences in detecting extrahepatic disease of NETs on routine liver magnetic resonance imaging (MRI).MethodOne hundred twenty-seven patients with NETs with and without hepatic and extrahepatic metastases who underwent liver MRI and SSTR-PET/CT were retrospectively analyzed. Two radiologists evaluated in consensus in four sessions: (1) non-contrast T1w+T2w (NC), (2) NC+DWI, (3) NC+ contrast-enhanced T1w (CE), and (4) NC+DWI+CE the presence and number of metastases (lymph nodes, bone, peritoneal surface, lung base, and abdominal organ). Sensitivity, specificity, positive, and negative predictive value for detection of metastases were calculated for each session in a patient-based manner; detection and error rates were calculated for lesion-based analysis. Comparison between the MR-sessions and positron emission tomography–computed tomography (PET/CT) was performed with the McNemar test.ResultsRegarding all 1,094 lesions detected in PET/CT, NC+DWI, and NC, CE+DWI identified most true-positive lesions 779 (71%) and 775 (71%), respectively. Patient-based analysis revealed significantly higher sensitivity by NC+DWI (85%) than NC and NC+CE (p = 0.011 and 0.004, respectively); the highest specificity was reached by NC+CE+DWI (100%). Site-based analysis revealed highest detection rates for lymph node metastases for NC+DWI and NC, CE+DWI (73 and 76%, respectively); error rates were lower for NC, CE+DWI with 5% compared with 17% (NC+DWI). Detection rates for bone metastases were similarly high in NC+DWI and NC, CE+DWI (75 and 74%, respectively), while CE showed no benefit. For peritoneal metastases highest sensitivity was reached by NC+DWI (67%).ConclusionThe combination of NC+DWI showed better sensitivities than the combination of NC+CE. NC+DWI showed similar, sometimes even better sensitivities than NC+CE+DWI, but with lower specificities