Cholecystitis induced by Yttrium-90 radioembolization of advanced liver tumors: prospective evaluation of a management algorithm in 197 consecutive patients.

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.

Enhancing the differentiation of pulmonary lymphoma and fungal pneumonia in hematological patients using texture analysis in 3-T MRI.

OBJECTIVES: To evaluate texture analysis in nonenhanced 3-T MRI for differentiating pulmonary fungal infiltrates and lymphoma manifestations in hematological patients and to compare the diagnostic performance with that of signal intensity quotients ("nonenhanced imaging characterization quotients," NICQs). METHODS: MR scans were performed using a speed-optimized imaging protocol without an intravenous contrast medium including axial T2-weighted (T2w) single-shot fast spin-echo and T1-weighted (T1w) gradient-echo sequences. ROIs were drawn within the lesions to extract first-order statistics from original images using HeterogeneityCAD and PyRadiomics. NICQs were calculated using signal intensities of the lesions, muscle, and fat. The standard of reference was histology or clinical diagnosis in follow-up. Statistical testing included ROC analysis, clustered ROC analysis, and DeLong test. Intra- and interrater reliability was tested using intraclass correlation coefficients (ICC). RESULTS: Thirty-three fungal infiltrates in 16 patients and 38 pulmonary lymphoma manifestations in 19 patients were included. Considering the leading lesion in each patient, diagnostic performance was excellent for T1w entropy (AUC 80.2%; p < 0.005) and slightly inferior for T2w energy (79.9%; p < 0.005), T1w uniformity (79.6%; p < 0.005), and T1w energy (77.0%; p < 0.01); the best AUC for NICQs was 72.0% for T2NICQmean (p < 0.05). Intra- and interrater reliability was good to excellent (ICC > 0.81) for these parameters except for moderate intrarater reliability of T1w energy (ICC = 0.64). CONCLUSIONS: T1w entropy, uniformity, and energy and T2w energy showed the best performances for differentiating pulmonary lymphoma and fungal pneumonia and outperformed NICQs. Results of the texture analysis should be checked for their intrinsic consistency to identify possible incongruities of single parameters. KEY POINTS: • Texture analysis in nonenhanced pulmonary MRI improves the differentiation of pulmonary lymphoma and fungal pneumonia compared with signal intensity quotients. • T1w entropy, uniformity, and energy along with T2w energy show the best performances for differentiating pulmonary lymphoma from fungal pneumonia. • The results of the texture analysis should be checked for their intrinsic consistency to identify possible incongruities of single parameters.

Benefit of Static FET PET in Pretreated Pediatric Brain Tumor Patients with Equivocal Conventional MRI Results.

BACKGROUND: MRI has shortcomings in differentiation between tumor tissue and post-therapeutic changes in pretreated brain tumor patients. PATIENTS: We assessed 22 static FET-PET/CT-scans of 17 pediatric patients (median age 12 years, range 2-16 years, ependymoma n=4, medulloblastoma n=4, low-grade glioma n=6, high-grade glioma n=3, germ cell tumor n=1, choroid plexus tumor n=1, median follow-up: 112 months) with multimodal treatment. METHOD: FET-PET/CT-scans were analyzed visually by 3 independent nuclear medicine physicians. Additionally quantitative FET-Uptake for each lesion was determined by calculating standardized uptake values (SUVmaxT/SUVmeanB, SUVmeanT/SUVmeanB). Histology or clinical follow-up served as reference. RESULTS: Static FET-PET/CT reliably distinguished between tumor tissue and post-therapeutic changes in 16 out of 17 patients. It identified correctly vital tumor tissue in 13 patients and post-therapeutic changes in 3 patients. SUV-based analyses were less sensitive than visual analyses. Except from a choroid plexus carcinoma, all tumor entities showed increased FET-uptake. DISCUSSION: Our study comprises a limited number of patients but results corroborate the ability of FET to detect different brain tumor entities in pediatric patients and discriminate between residual/recurrent tumor and post-therapeutic changes. CONCLUSIONS: We observed a clear benefit from additional static FET-PET/CT-scans when conventional MRI identified equivocal lesions in pretreated pediatric brain tumor patients. These results warrant prospective studies that should include dynamic scans.

Comparing HCC arterial tumour vascularisation on baseline imaging and after lipiodol cTACE: how do estimations of enhancing tumour volumes differ on contrast-enhanced MR and CT?

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. KEY POINTS: • 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.

Biliary duct stenosis after image-guided high-dose-rate interstitial brachytherapy of central and hilar liver tumors : A systematic analysis of 102 cases.

OBJECTIVE: Image-guided high-dose-rate interstitial brachytherapy (iBT) with iridium-192 is an effective treatment option for patients with liver malignancies. Little is known about long-term radiation effects on the bile duct system when central hepatic structures are exposed to iBT. This retrospective analysis investigates the occurrence of posthepatic cholestasis (PHC) and associated complications in patients undergoing iBT. MATERIALS AND METHODS: We identified patients who underwent iBT of hepatic malignancies and had point doses of ≥1 Gy to central bile duct structures. Patients with known bile duct-related diseases or prior bile duct manipulation were excluded. RESULTS: 102 patients were retrospectively included. Twenty-two patients (22%) developed morphologic PHC after a median of 17 (3-54) months; 18 of them were treated using percutaneous transhepatic cholangiopancreatography drainage or endoscopic retrograde cholangiopancreatography. The median point dose was 24.8 (4.4-80) Gy in patients with PHC versus 14.2 (1.8-61.7) Gy in those without PHC (p = 0.028). A dose of 20.8 Gy (biological effective dose, BED3/10 = 165/64.1 Gy) was identified to be the optimal cutoff dose (p = 0.028; 59% sensitivity, 24% specificity). Abscess/cholangitis was more common in patients with PHC compared to those without (4 of 22 vs. 2 of 80; p = 0.029). Median survival did not differ between patients with and without PHC (43 vs. 36 months; p = 0.571). CONCLUSION: iBT of liver malignancies located near the hilum can cause PHC when the central bile ducts are exposed to high point doses. Given the long latency and absence of impact of iBT-induced PHC on median survival, the rate of cholestasis and complications seen in our patients appears to be acceptable.

Confirmation of the prognostic value of pretherapeutic tumor SUR and MTV in patients with esophageal squamous cell carcinoma.

PURPOSE: The prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. In a recent publication, we were able to show that PET can provide independent prognostic information in such a patient group and that the tumor-to-blood standard uptake ratio (SUR) can improve the prognostic value of tracer uptake values. The present investigation addresses the question of whether the distinctly improved prognostic value of SUR can be confirmed in a similar patient group that was examined and treated at a different site. METHODS: 18F-FDG PET/CT was performed in 147 consecutive patients (115 male, 32 female, mean age: 62 years) with newly diagnosed esophageal squamous cell carcinoma prior to definitive radiochemotherapy. In the PET images, the metabolic active volume (MTV) of the primary tumor was delineated with an adaptive threshold method. For the resulting ROIs, SUVmax and total lesion glycolysis (TLG = MTV × SUVmean) were computed. The blood SUV was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as ratio of tumor SUV and blood SUV. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant-metastases-free survival (DM), and locoregional control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. RESULTS: Univariate Cox regression revealed MTV, TLG, and SURmax as significant prognostic factors for OS. MTV as well as TLG were significant prognostic factors for LRC while SURmax showed only a trend for significance. None of the PET parameters was prognostic for DM. In univariate analysis, SUVmax was not prognostic for any of the investigated clinical endpoints. In multivariate analysis (T-stage, N-stage, MTV, and SURmax), MTV was an independent prognostic factor for OS and showed a trend for significance for LRC. SURmax was not an independent predictor for OS or LRC. When including the PET parameters separately in multivariate analysis, MTV as well as SURmax were prognostic factors for OS indicating that SURmax is independent from the clinical parameters but not from MTV. In addition, MTV was an independent prognostic factor for LRC in this separate analysis. CONCLUSIONS: Our study revealed a clearly improved prognostic value of tumor SUR compared to tumor SUV and confirms our previously published findings regarding OS. Furthermore, SUR delivers prognostic information beyond that provided by the clinical parameters alone, but does not add prognostic information beyond that provided by MTV in this patient group. Therefore, our results suggest that pretherapeutic MTV is the parameter of choice for PET-based risk stratification in the considered setting but further investigations are necessary to demonstrate that this suggestion is correct.

Age-dependent diagnostic accuracy of clinical scoring systems and D-dimer levels in the diagnosis of pulmonary embolism with computed tomography pulmonary angiography (CTPA).

OBJECTIVE: The aim of this study was to compare the age-dependent diagnostic performance of clinical scores and D-dimer testing to identify patients with suspected pulmonary embolism (PE). METHODS: Consecutive patients with suspected PE referred from the emergency department for computed tomography pulmonary angiography (CTPA) were retrospectively evaluated. Diagnostic scores (classic Wells score (WS), modified WS, simplified WS, revised Geneva score (GS), simplified GS, and YEARS score) were calculated from medical records. Results of D-dimer testing were retrieved from the laboratory database. CTPA was the diagnostic reference standard. Four age groups were analyzed (< 50, 50-64, 65-74, and ≥ 75 years). Statistical analysis used receiver operating characteristics as well as uni- and multivariate analyses with calculation of prediction models. The study was IRB approved. RESULTS: One thousand consecutive patients were included. Areas under the curve (AUC) and accuracies were superior in patients < 50 years. For the classic WS, the AUC decreased by 11% with the optimal cutoff dropping 1.5 points in patients ≥ 75 years; for D-dimer levels, the optimal cutoff was 900 µg/L higher in both ≥ 65 years groups with a max. decrease of the AUC of 9%. In terms of accuracy, the YEARS score performed best across all groups. Classic WS and D-dimer level showed a significant interaction with patient age in prediction models. CONCLUSION: D-dimer measurement and clinical scores perform best in patients < 50 years. The YEARS score performs best across all age groups and is therefore recommended. KEY POINTS: • The probability of pulmonary embolism predicted by fibrin fibrinogen degradation products and clinical scores shows the highest accuracy in patients < 50 years. • The probability of pulmonary embolism predicted by the YEARS score shows the highest accuracy in each age group. • Classic Wells score and fibrin fibrinogen degradation products show a significant interaction with patient age in a logistic regression model.

Predicting liver failure after extended right hepatectomy following right portal vein embolization with gadoxetic acid-enhanced MRI.

OBJECTIVES: Predicting post-hepatectomy liver failure (PHLF) after extended right hepatectomy following portal vein embolization (PVE) from serial gadoxetic acid-enhanced magnetic resonance imaging (MRI). METHODS: Thirty-six patients who underwent hepatectomy following PVE were evaluated prospectively with gadoxetic acid-enhanced MRI examinations at predefined intervals during the course of their treatment, i.e., before and 14 days and 28 days after PVE as well as 10 days after hepatectomy. Relative enhancement (RE) and volume of the left and right liver lobes were determined. The study population was divided into two groups with respect to signs of PHLF. Differences between the two groups were assessed using the Mann-Whitney U test, and predictive parameters for group membership were investigated using ROC and logistic regression analysis. RESULTS: RE of the left lobe prior to PVE versus 14 days after PVE was significantly lower in patients with PHLF than in those without PHLF (Mann-Whitney U test p < 0.001) and proved to be the best predictor of PHLF in ROC analysis with an AUC of 0.854 (p < 0.001) and a cutoff value of - 0.044 with 75.0% sensitivity and 92.6% specificity. Consistent with this result, logistic linear regression analysis adjusted for age identified the same parameter to be a significant predictor of PHLF (p = 0.040). CONCLUSIONS: Gadoxetic acid-enhanced MRI performed as an imaging-based liver function test before and after PVE can help to predict PHLF. The risk of PHLF can be predicted as early as 14 days after PVE. KEY POINTS: • To predict the likelihood of post-hepatectomy liver failure, it is important to estimate not only future liver remnant volume prior to extended liver resection but also future liver remnant function. • Future liver remnant function can be predicted by performing gadoxetic acid-enhanced MRI as an imaging-based liver function test before and after portal vein embolization. • A reduction of relative enhancement of the liver in gadoxetic acid-enhanced MRI after portal vein embolization of 0.044 predicts post-hepatectomy liver failure with 75.0% sensitivity and 92.6% specificity.

Magnetic resonance imaging features of craniofacial fibrous dysplasia.

PURPOSE: To assess the value of magnetic resonance imaging (MRI) in detecting craniofacial fibrous dysplasia (CFD) and diagnosing and differentiating it from intraosseous meningioma. Additionally, the MRI appearance of the typical computed tomography (CT) imaging feature, the ground glass phenomenon, was evaluated. MATERIAL AND METHODS: MRI datasets of 32 patients with CFD were analysed retrospectively. Detectability in MRI was assessed by analysis of 10 randomly selected patients with CFD and 10 normal controls by two blinded readers. Changes of affected bone, internal lesion structure, T1 and T2 signal intensity, and contrast enhancement of the lesion in general and ground glass areas in particular were assessed. Ten patients with intraosseous meningioma (one in each) served as differential diagnosis for CFD. RESULTS: All 10 CFD lesions were reliably detected in MRI. In 32 patients 36 CFD lesions were evaluated. In 66.7% CFD were iso- to hypointense in T1 and hyperintense in T2; this proportion was similar for ground glass areas (65.7%). Ground glass areas were more homogeneously structured than the whole CFD lesion in both T1 (100% vs. 56%, respectively) and T2 (91% vs. 61%, respectively). Contrast enhancement was found in 97% of complete CFD lesions and 93% of ground glass areas. The accuracy for CFD vs. intraosseous meningioma was 100% for 'no soft-tissue component' and 98% for 'bone broadening' in MRI. CONCLUSIONS: Distinct morphological changes of CFD are reliably detected in MRI and allow differentiation from intraosseous meningioma. Areas with ground glass phenomenon in CT show a predominantly homogenous internal structure in MRI with contrast enhancement.

Mesenteric Fibrosis in Midgut Neuroendocrine Tumors: Functionality and Radiological Features.

BACKGROUND: Mesenteric fibrosis (MF) surrounding a lymph node metastasis is a known phenomenon in midgut neuroendocrine tumors (NETs) with characteristic radiological appearance. Its etiology is poorly understood as it affects some but not all midgut NET patients with lymphatic involvement. This study assessed a potential relationship of MF with carcinoid syndrome, urinary 5-hydroxyindoleacetic acid (5-HIAA), and carcinoid heart disease (CHD). METHODS: A cohort of 81 patients with pathologically proven NETs with the primary site in the midgut and mesenteric lymphatic metastases on imaging were retrospectively included. Imaging characteristics of lymphatic and hepatic metastases at diagnosis (size, number, burden, and morphologic features, including presence of MF), Ki67 grading, 5-HIAA, functionality, and development of CHD were analyzed. RESULTS: Overall, 54% of patients had MF. The presence of MF was more frequently associated with mesenteric vessel encasement (100 vs. 46% without MF; p < 0.001), presence of hepatic metastases (91 vs. 62%; p = 0.002), larger hepatic tumor burden (15 vs. 5%; p = 0.001), and functionality (86 vs. 43%; p < 0.001). Multivariate analysis revealed 5-HIAA ≥395 µmol/day (p = 0.020), age (p = 0.013), and largest lymphatic metastasis ≥24 mm (p = 0.009) as independent predictors of MF, while functionality (p = 0.098) and CHD (p = 0.070) showed a tendency towards significance. MF was associated with decreased time to development of CHD in functional midgut NETs (p = 0.043). CONCLUSIONS: We found a significant association of MF with metastatic patterns and with criteria of functionality. The association of MF with elevated 5-HIAA, and consecutively with carcinoid syndrome and potential development of CHD, suggests a linked pathophysiological mechanism, which might be similar to that of endocardial fibrosis.

Is There Long-term Signal Intensity Increase in the Central Nervous System on T1-weighted Images after MR Imaging with the Hepatospecific Contrast Agent Gadoxetic Acid? A Cross-sectional Study in 91 Patients.

Purpose To evaluate whether there is T1-weighted signal intensity (SI) increase in the dentate nucleus (DN) and globus pallidus (GP) in relation to the middle cerebellar peduncle (MCP), pons, and thalamus after repeated administration of the liver-specific contrast agent gadoxetic acid. Materials and Methods This was an institutional review board-approved, prospectively conducted (written informed consent acquired), cross-sectional study performed in a consecutively selected patient group (n = 91; patients received one to 37 doses of gadoxetic acid) and a control group (n = 52; subjects had never received injections of gadolinium-based contrast agent) examined with a standard T1-weighted two-dimensional spin-echo pulse sequence of the brain at 1.5 T. DN/MCP, DN-to-pons, GP-to thalamus, and GP-to-cerebrospinal fluid ratios were measured and compared by using the nonparametric Kruskal-Wallis test, corresponding pairwise tests, and Spearman correlation. Results DN/MCP (ρ = 0.51, P < .0001) and DN-to-pons (ρ = 0.41, P = .0001) ratios correlated positively with the number of previous administrations of gadoxetic acid. DN/MCP and DN-to-pons ratios were significantly different between control subjects (medians of 1.016 and 1.034, respectively) and patients with more than 10 gadoxetic acid administrations (1.038 [P < .0001] and 1.053 [P = .0100], respectively), whereas no significant difference was found in the groups with five to 10 (1.029 [P = .053] and 1.044 [P = .072], respectively) and fewer than five (1.014 [P = .420] and 1.030 [P = .595], respectively) gadoxetic acid administrations. GP-to-thalamus ratios differed significantly between the study and control groups (P < .0001), whereas no significant correlation was found for GP-to-thalamus ratios and number of gadoxetic acid administrations (ρ = 0.13, P = .2304). Conclusion Results show a significant correlation between the number of gadoxetic acid administrations and the increase of SI in the DN, which is likely due to gadolinium retention. © RSNA, 2017.

Initial Experience with CT-Guided High-Dose-Rate Brachytherapy in the Multimodality Treatment of Neuroendocrine Tumor Liver Metastases.

PURPOSE: To evaluate efficacy of computed tomography (CT)-guided high-dose-rate brachytherapy (HDRBT) of neuroendocrine liver metastases (NELM) with the goal of local tumor control (LTC). MATERIALS AND METHODS: This retrospective study included all patients with unresectable NELM treated with CT-guided HDRBT between January 2007 and April 2015. Magnetic resonance imaging follow-up was performed 6 weeks after ablation and then every 3 months. The primary endpoint was LTC. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and complications. RESULTS: In 27 patients, 52 NELM were treated in 40 sessions. Three patients (11.1%) developed local progression with LTC of 1.9-36.8 months (median 10.4 months, mean 16.4 months). The remaining 24 patients (89.9%) had LTC of 3.1-106.1 months (median 31.3 months, mean 32.6 months). Progression or death was observed in 19 patients (70.4%) with PFS of 1.9-55.3 months (median 7.3 months, mean 16.3 months); the remaining 8 patients (29.6%) had PFS of 3.7-50.1 months (median 13.4 months, mean 19.6 months). Four patients (14.8%) died of causes unrelated to the procedure; their OS was 11.7-52.3 months (median 48.7 months, mean 40.4 months). OS was 4.2-106.1 months (median 30.3 months, mean 34.1 months) in the 23 surviving patients (85.2%). One patient experienced pain with nausea and vomiting, and 1 patient with biliodigestive anastomosis had a hepatic abscess. CONCLUSION: CT-guided HDRBT is a promising therapy with excellent LTC rates and low morbidity for patients with isolated/oligometastatic NELM.

Non-traumatic incidental findings in patients undergoing whole-body computed tomography at initial emergency admission.

OBJECTIVE: To evaluate the number, localisation and importance of non-traumatic incidental findings (IFs) in patients with suspected or obvious multiple trauma undergoing whole-body CT (WBCT) in a level-1 trauma centre. METHODS: Between January 2009 and December 2013, a total of 2440 patients with trauma undergoing WBCT at admission to a level-1 trauma centre of a university hospital were retrospectively analysed, through imaging IFs unrelated to trauma with the radiological reports. All IFs were grouped into four categories according to their clinical relevance. Category 1: urgent treatment or further clarification needed; category 2: further examination and follow-up within 3-6 months required; category 3: findings with no immediate consequences for the treatment of the patient but of potential relevance in the future; category 4: harmless findings. RESULTS: Altogether, 5440 IFs in 2440 patients (1735 male, 705 female; mean age 45.1 years) were documented. In 204 patients (8.4%) urgent category 1 findings were reported, 766 patients (31.4%) had category 2 findings, 1236 patients (50.7%) had category 3 findings and 1173 patients (48.1%) had category 4 findings. Most IFs were detected in the abdomen/pelvis (42.5%). 602 (24.7%) of the patients had no IFs. CONCLUSIONS: WBCT scans of unrelated trauma patients demonstrate a high rate of IF. A substantial percentage (8.4%) of patients had urgent category 1IFs and a high percentage (31.4%) had category 2 IFs requiring a follow-up. This high number of patients with polytrauma undergoing WBCT, having IFs of high relevance, poses a major challenge for the level-1 trauma centre in the acute and postacute management of these patients.

The asphericity of the metabolic tumour volume in NSCLC: correlation with histopathology and molecular markers.

PURPOSE: Asphericity (ASP) is a tumour shape descriptor based on the PET image. It quantitates the deviation from spherical of the shape of the metabolic tumour volume (MTV). In order to identify its biological correlates, we investigated the relationship between ASP and clinically relevant histopathological and molecular signatures in non-small-cell lung cancer (NSCLC). METHODS: The study included 83 consecutive patients (18 women, aged 66.4 ± 8.9 years) with newly diagnosed NSCLC in whom PET/CT with 18F-FDG had been performed prior to therapy. Primary tumour resection specimens and core biopsies were used for basic histopathology and determination of the Ki-67 proliferation index. EGFR status, VEGF, p53 and ALK expression were obtained in a subgroup of 44 patients. The FDG PET images of the primary tumours were delineated using an automatic algorithm based on adaptive thresholding taking into account local background. In addition to ASP, SUVmax, MTV and some further descriptors of shape and intratumour heterogeneity were assessed as semiquantitative PET measures. RESULTS: SUVmax, MTV and ASP were associated with pathological T stage (Kruskal-Wallis, p = 0.001, p < 0.0005 and p < 0.0005, respectively) and N stage (p = 0.017, p = 0.003 and p = 0.002, respectively). Only ASP was associated with M stage (p = 0.026). SUVmax, MTV and ASP were correlated with Ki-67 index (Spearman's rho = 0.326/p = 0.003, rho = 0.302/p = 0.006 and rho = 0.271/p = 0.015, respectively). The latter correlations were considerably stronger in adenocarcinomas than in squamous cell carcinomas. ASP, but not SUVmax or MTV, showed a tendency for a significant association with the extent of VEGF expression (p = 0.058). In multivariate Cox regression analysis, ASP (p < 0.0005) and the presence of distant metastases (p = 0.023) were significantly associated with progression-free survival. ASP (p = 0.006), the presence of distant metastases (p = 0.010), and Ki-67 index (p = 0.062) were significantly associated with overall survival. CONCLUSION: The ASP of primary NSCLCs on FDG PET images is associated with tumour dimensions and molecular markers of proliferation and angiogenesis.

Y90 Radioembolization in chemo-refractory metastastic, liver dominant colorectal cancer patients: outcome assessment applying a predictive scoring system.

BACKGROUND: In treatment-refractory liver dominant metastatic colorectal cancer, the role of liver directed therapies still is unclear. We sought to determine a prognostic score for Y90 radioembolization in these patients. METHODS: We analyzed 106 patients with refractory liver dominant mCRC who had undergone a total of 178 Y90 radioembolizations with resin microspheres was collected. Potential factors influencing survival were analyzed using a Cox regression. The Log rank test served to establish prognostic factors and to form a clinical score for outcome prediction after Y90 radioembolization. RESULTS: Median survival of all patients was 6.7 months. Neither age nor prior surgical or systemic therapy nor metastatic spread had an effect on survival. In contrast, hepatic tumor load, Karnofsky index as well as CEA and CA19-9 serums level had a significant influence (p < 0.001, p = 0.037, p = 0.023 and p < 0.001, respectively). These three factors formed a score with 1 point each for tumor load >20 %, CEA >130 ng/ml or CA19-9 > 200U/ml and Karnofsky index <80 %. Patients with a score of 0 and 1 displayed a median OS of 10.4 months. Patients with a score of 2 and 3 demonstrated a median OS of 5.1 months only (p < 0.001). CONCLUSION: Overaggressive patient selection for Y90 radioembolization of liver dominant chemorefractory mCRC is of questionable benefit. A scoring system comprising hepatic tumor load, CEA and CA19-9 serum levels and Karnofsky index (TuCK-score) may support an improved patient selection. In our cohort of liver only versus liver dominant disease, extrahepatic lung or lymphatic metastases did not significantly alter the prognosis.

Dual time point imaging for F18-FDG-PET/CT does not improve the accuracy of nodal staging in non-small cell lung cancer patients.

OBJECTIVES: To analyze the diagnostic performance of dual time point imaging (DTPI) for pre-therapeutic lymph node (LN) staging in non-small cell lung cancer (NSCLC). METHODS: This was a retrospective analysis of 47 patients with NSCLC who had undergone DTPI by PET (early + delayed) using F18-fluorodeoxyglucose (FDG). PET raw data were reconstructed iteratively (point spread function + time-of-flight). LN uptake in PET was assessed visually (four-step score) and semi-quantitatively (SUVmax, SUVmean, ratios LN/primary, LN/liver, and LN/mediastinal blood pool). DTPI analyses included retention indices (RIs), Δ-ratios and changes in visual score. Histology or cytology served as standards of reference. Accuracy was determined based on ROC analyses. RESULTS: Thirty-six of 155 LNs were malignant. DTPI accuracy was low for all measures (visual assessment, 24.5%; RI SUVmax, 68.4%; RI SUVmean, 65.8%; Δ-ratios, 63.9-76.1%) and significantly inferior to early PET. Accuracies of early (range, 86.5-92.9%) and delayed PET (range, 85.2-92.9%) were comparable. At early PET, accuracy of the visual score (92.9%) was similar or superior to semi-quantitative analyses (range, 86.5-92.3%). CONCLUSIONS: Using a modern PET/CT device and novel image reconstruction, neither additional delayed PET nor DTPI analyses improved the accuracy of PET-based LN staging. Dedicated visual assessment criteria performed very well. KEY POINTS: • DTPI did not improve accuracy of PET-based LN staging in NSCLC. • Analyzed SUV ratios were not superior to LN SUVmax or SUVmean. • A four-step visual score may allow highly accurate, standardized LN assessment.

Increased evidence for the prognostic value of primary tumor asphericity in pretherapeutic FDG PET for risk stratification in patients with head and neck cancer.

PURPOSE: In a previous study, we demonstrated the first evidence that the asphericity (ASP) of pretherapeutic FDG uptake in the primary tumor provides independent prognostic information in patients with head and neck cancer. The aim of this work was to confirm these results in an independent patient group examined at a different site. METHODS: FDG-PET/CT was performed in 37 patients. The primary tumor was delineated by an automatic algorithm based on adaptive thresholding. For the resulting ROIs, the metabolically active part of the tumor (MTV), SUVmax, SUVmean, total lesion glycolysis (TLG) and ASP were computed. Univariate Cox regression with respect to progression free survival (PFS) and overall survival (OS) was performed. For survival analysis, patients were divided in groups of high and low risk according to the parameter cut-offs defined in our previous work. In a second step, the cut-offs were adjusted to the present data. Univariate and multivariate Cox regression was performed for the pooled data consisting of the current and the previously described patient group (N = 68). In multivariate Cox regression, clinically relevant parameters were included. RESULTS: Univariate Cox regression using the previously published cut-off values revealed TLG (hazard ratio (HR) = 3) and ASP (HR = 3) as significant predictors for PFS. For OS MTV (HR = 2.7) and ASP (HR = 5.9) were significant predictors. Using the adjusted cutoffs MTV (HR = 2.9/3.3), TLG (HR = 3.1/3.3) and ASP (HR = 3.1/5.9) were prognostic for PFS/OS. In the pooled data, multivariate Cox regression revealed a significant prognostic value with respect to PFS/OS for MTV (HR = 2.3/2.1), SUVmax (HR = 2.1/2.5), TLG (HR = 3.5/3.6), and ASP (HR = 3.4/4.4). CONCLUSIONS: Our results confirm the independent prognostic value of ASP of the pretherapeutic FDG uptake in the primary tumor in patients with head and neck cancer. Moreover, these results demonstrate that ASP can be determined unambiguously across different sites.

Locally ablative treatment of breast cancer liver metastases: identification of factors influencing survival (the Mammary Cancer Microtherapy and Interventional Approaches (MAMMA MIA) study).

BACKGROUND: Liver metastases from breast cancer (LMBC) are typically considered to indicate systemic disease spread and patients are most often offered systemic palliative treatment only. However, retrospective studies suggest that some patients may have improved survival with local treatment of their liver metastases compared to systemic therapy alone. In the absence of randomized trials, it is important to identify patient characteristics indicating that benefit from local treatment can be expected. METHODS: 59 patients undergoing radiofrequency ablation (RFA), interstitial brachytherapy (BT), or radioembolization (RE) of LMBC as a salvage treatment were studied. Potential factors influencing survival were analyzed in a multivariate Cox model. For factors identified to have an independent survival impact, Kaplan-Meier analysis and comparison of overall survival (OS) using the log-rank test was performed. RESULTS: Median OS following local interventional treatment was 21.9 months. Considering only factors evaluable at treatment initiation, maximum diameter of liver metastases (≥3.9 cm; HR: 3.1), liver volume (≥ 1376 mL; HR: 2.3), and history of prior chemotherapy (≥ 3 lines of treatment; HR: 2.5-2.6) showed an independent survival impact. When follow-up data were included in the analysis, significant factors were maximum diameter of liver metastases (≥ 3.9 cm; HR: 3.1), control of LMBC during follow-up (HR: 0.29), and objective response as best overall response (HR: 0.21). Neither the presence of any extrahepatic metastases nor presence of bone metastases only had a significant survival impact. Median OS was 38.7 vs. 16.1 months in patients with metastases < vs. ≥ 3.9 cm, 36.6 vs. 10.2 months for patients having objective response vs. stable/progressive disease, and 38.5 vs. 14.2 months for patients having controlled vs. non-controlled disease at follow-up. CONCLUSION: Local control of LMBC confers a survival benefit and local interventional treatment for LMBC should be studied in a randomized trial. Patients with small metastases and limited history of systemic LMBC treatment are most likely to benefit from local approaches. Limited extrahepatic disease should not lead to exclusion from a randomized study and should not be a contraindication for local LMBC treatment as long as no randomized data are available.

Implications of imaging criteria for the management and treatment of intraductal papillary mucinous neoplasms - benign versus malignant findings.

OBJECTIVES: Evaluation of computed tomography (CT) and magnetic resonance imaging (MRI) for differentiation of pancreatic intraductal papillary mucinous neoplasm (IPMN) subtypes based on objective imaging criteria. METHODS: Fifty-eight patients with 60 histologically confirmed IPMNs were included in this retrospective study. Eighty-three imaging studies (CT,n = 42; MRI,n = 41) were analysed by three independent blinded observers (O1-O3), using established imaging criteria to assess likelihood of malignancy (-5, very likely benign; 5, very likely malignant) and histological subtype (i.e., low-grade (LGD), moderate-grade (MGD), high-grade dysplasia (HGD), early invasive carcinoma (IPMC), solid carcinoma (CA) arising from IPMN). RESULTS: Forty-one benign (LGD IPMN,n = 20; MGD IPMN,n = 21) and 19 malignant (HGD IPMN,n = 3; IPMC,n = 6; solid CA,n = 10) IPMNs located in the main duct (n = 6), branch duct (n = 37), or both (n = 17) were evaluated. Overall accuracy of differentiation between benign and malignant IPMNs was 86/92 % (CT/MRI). Exclusion of overtly malignant cases (solid CA) resulted in overall accuracy of 83/90 % (CT/MRI). The presence of mural nodules and ductal lesion size ≥30 mm were significant indicators of malignancy (p = 0.02 and p < 0.001, respectively). CONCLUSIONS: Invasive IPMN can be identified with high confidence and sensitivity using CT and MRI. The diagnostic problem that remains is the accurate radiological differentiation of premalignant and non-invasive subtypes. KEY POINTS: • CT and MRI can differentiate benign from malignant forms of IPMN. • Identifying (pre)malignant histological IPMN subtypes by CT and MRI is difficult. • Overall, diagnostic performance with MRI was slightly (not significantly) superior to CT.

CT-guided Interstitial Brachytherapy of Hepatocellular Carcinoma before Liver Transplantation: an Equivalent Alternative to Transarterial Chemoembolization?

OBJECTIVES: Transarterial chemoembolization (TACE) is established as bridging therapy of HCC listed for transplantation (LT). CT-guided brachytherapy (CTB) has not been evaluated as a bridging concept. We compared CTB and TACE for bridging before LT in HCC patients. METHODS: Twelve patients with HCC received LT after CTB (minimal tumour dose, 15-20 Gy). Patients were matched (CTB:TACE, 1:2) by sex, age, number and size of lesions, and underlying liver disease with patients who received TACE before transplantation. Study endpoints were extent of necrosis at histopathology and recurrence rate after OLT. RESULTS: There were no significant differences between the CTB and TACE groups regarding Child-Pugh category (p = 0.732), AFP (0.765), time on waiting list (p = 0.659), number (p = 0.698) and size (p = 0.853) of HCC lesions, fulfilment of Milan-criteria (p = 0.638), or previous liver-specific treatments. CTB achieved higher tumour necrosis rates than TACE (p = 0.018). The 1- and 3-year recurrence rate in the CTB group was 10 and 10 % vs. TACE, 14 and 30 % (p = 0.292). CONCLUSIONS: Our data show comparable or even better response and post-LT recurrence rates of CTB compared to TACE for treating HCC in patients prior to LT. CTB should be further evaluated as an alternative bridging modality, especially for patients not suited for TACE. KEY POINTS: • CT-guided interstitial brachytherapy (CTB) is a promising alternative to transarterial chemoembolization (TACE). • CTB instead of TACE is possible for bridging to liver transplantation in HCC patients. • HCC recurrence was not associated with CTB despite potential tumour seeding.