Timm Denecke

Positron Emission Tomography for Staging of Pediatric Sarcoma Patients: Results of a Prospective Multicenter Trial

PURPOSE The objective of this study was to evaluate the impact of positron emission tomography (PET) using fluorine-18-fluorodeoxyglucose (FDG) for initial staging and therapy planning in pediatric sarcoma patients. PATIENTS AND METHODS In this prospective multicenter study, 46 pediatric patients (females, n = 22; males, n = 24; age range, 1 to 18 years) with histologically proven sarcoma (Ewing sarcoma family tumors, n = 23; osteosarcoma, n = 11; rhabdomyosarcoma, n = 12) were examined with conventional imaging modalities (CIMs), including ultrasound, computed tomography (CT), magnetic resonance imaging, and bone scintigraphy according to the standardized algorithms of the international therapy optimization trials, and whole-body FDG-PET. A lesion- and patient-based analysis of PET alone and CIMs alone and a side-by-side (SBS) analysis of FDG-PET and CIMs were performed. The standard of reference consisted of all imaging material, follow-up data (mean follow-up time, 24 +/- 12 months), and histopathology and was determined by an interdisciplinary tumor board. RESULTS FDG-PET and CIMs were equally effective in the detection of primary tumors (accuracy, 100%). PET was superior to CIMs concerning the correct detection of lymph node involvement (sensitivity, 95% v 25%, respectively) and bone manifestations (sensitivity, 90% v 57%, respectively), whereas CT was more reliable than FDG-PET in depicting lung metastases (sensitivity, 100% v 25%, respectively). The patient-based analysis revealed the best results for SBS, with 91% correct therapy decisions. This was significantly superior to CIMs (59%; P < .001). CONCLUSION In staging pediatric sarcoma, subsidiary FDG-PET scanning depicts important additional information and has a relevant impact on therapy planning when analyzed side-by-side with CIMs.

ENETS Consensus Guidelines for the Management of Patients with Neuroendocrine Neoplasms from the Jejuno-Ileum and the Appendix Including Goblet Cell Carcinomas

a Division of Hepatology and Gastroenterology, Department of Internal Medicine, Campus Virchow-Klinikum, Charite-Universitatsmedizin Berlin, Berlin , Germany; b Department of Pathology, Universitatsspital, Zurich , Switzerland; c Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; d Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem , Israel; e Department of Internal Medicine, Philipps University, Marburg , Germany; f Hopital Sirio Libanes, Centro de Oncologia, Sao Paulo , Brazil; g Department of Radiology, Campus Virchow-Klinikum, Charite, University Medicine Berlin, Berlin , Germany; h Department of Oncology, Institut Catala d’Oncologia (IDIBELL), Barcelona , Spain; i Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford , UK

Suspected Chronic Myocarditis at Cardiac MR: Diagnostic Accuracy and Association with Immunohistologically Detected Inflammation and Viral Persistence

PURPOSE To retrospectively compare the diagnostic accuracy of three cardiac magnetic resonance (MR) imaging approaches for the detection of histologic and immunohistologic criteria (reference standard) proved myocardial inflammation in patients clinically suspected of having chronic myocarditis (CMC). MATERIALS AND METHODS Cardiac MR imaging was performed in 83 consecutive patients (55 male, 28 female; mean age, 44.8 years +/- 17.7 [standard deviation]) clinically suspected of having CMC, after written informed consent was obtained according to guidelines of the local ethics committee, which approved the study. T2-weighted triple-inversion-recovery imaging to calculate the edema ratio (ER), T1-weighted imaging before and after contrast agent administration to calculate the myocardial global relative enhancement (gRE), and inversion-recovery gradient-echo imaging to evaluate areas of late gadolinium enhancement (LE) were performed. The MR results were correlated with the endomyocardial biopsy (EMB) findings to detect intramyocardial inflammation and cardiotropic viral genomes analyzed at polymerase chain reaction assay. For statistical analyses, receiver operating characteristic analysis and the Wilcoxon test for unpaired data were used because the Kolomogorov-Smirnov test revealed a distribution of data that was different from normality. RESULTS Intramyocardial inflammation and cardiotropic viral persistence were confirmed at immunohistologic analysis in 48 and 49 of the 83 patients, respectively. The sensitivity, specificity, and diagnostic accuracy of the MR parameters, as compared with the immunohistologic detection of inflammation, were, respectively, 62%, 86%, and 72% for gRE; 67%, 69%, and 68% for ER; and 27%, 80%, and 49% for LE. Cardiac MR-derived gRE, ER, and LE were not associated with polymerase chain reaction proof of viral genomes. CONCLUSION In patients clinically suspected of having CMC, increased gRE and ER indicating inflammation were common findings that could be confirmed at immunohistologic analysis, whereas LE had low sensitivity and accuracy. Cardiac MR imaging may be helpful in detecting intramyocardial inflammation noninvasively, but it fails to depict viral persistence.

Early and Late Therapy Response Assessment With [18F]Fluorodeoxyglucose Positron Emission Tomography in Pediatric Hodgkin's Lymphoma: Analysis of a Prospective Multicenter Trial

PURPOSE In adult Hodgkins lymphoma (HL) risk stratification after early therapy response assessment with [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) seems to allow tailoring therapy with less toxicity for patients with adequate metabolic response. This study delivers the first prospective data on the potential of FDG-PET for response assessment in pediatric HL. PATIENTS AND METHODS FDG-PET was performed in 40 pediatric HL patients before polychemotherapy (PET-1), after two cycles of polychemotherapy (PET-2), and after completion of polychemotherapy (PET-3). Mean follow-up was 46 months (range, 26 to 72 months). RESULTS At early and late response assessment, the proportion of PET-negative patients was significantly higher compared with those patients with negative findings in conventional imaging methods (CIMs; PET-2, 26 of 40 v CIM-2, one of 40; P < .001; PET-3, 21 of 29 v CIM-3, four of 29; P < .001). Sensitivity and negative predictive value were 100% for early and late therapy response assessment by PET. Both patients suffering a relapse during follow-up were identified by PET-2/3, whereas one of these patients was not detected by CIM-3. PET was superior to CIMs with regard to specificity in early and late therapy response assessment (68% v 3%, and 78% v 11%, respectively; both P < .001). Specificity of early therapy response assessment by PET was improved to 97% by quantitative analysis of maximal standardized uptake value reduction using a cutoff value of 58%. CONCLUSION Pediatric HL patients with a negative PET in response assessment have an excellent prognosis while PET-positive patients have an increased risk for relapse.

Impact of Multiphase 68Ga-DOTATOC-PET/CT on therapy management in patients with neuroendocrine tumors.

Aim: Retrospective evaluation of the impact of integrated positron emission tomography/computed tomography (PET/CT) using 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) on the therapeutic management of patients with neuroendocrine tumors (NET). Methods: The 68Ga-DOTATOC-PET/CT data of 66 patients (31 male, 35 female; age: 29–79, mean age: 56 years) with known or suspected NET were included. Imaging data (PET and triple-phase contrast-enhanced CT) were evaluated in consensus by two readers for the visualization of NET manifestations. Combined PET/CT, clinical and imaging follow-up as well as histopathology (if available) served as the reference standard. In order to assess the impact of the respective submodalities on the therapeutic strategy chosen, the results were compared to the treatment decision made by the interdisciplinary NET tumor board of our institution. Results: Two of the initial 66 patients included did not suffer from NET according to further immunohistopathological examination. In 50 of the remaining 64 (78%) NET patients, a total of 181 NET manifestations were detected by PET/CT. 59/181 (32.6%) were detected by one submodality only (CT 17.1%, PET 15.5%, p for comparison of both = 0.459). Combined PET/CT reading had an impact on the therapeutic management in 24 of 64 (38%) NET patients: primary resection (n = 5), curative lymph node resection (n = 1), initiation/switch of chemotherapy (CTx) due to progressive disease (n = 10), no surgery due to systemic disease (n = 2), radiopeptide receptor therapy instead of CTx (n = 1), additional bisphosphonate therapy (n = 4), and hepatic brachytherapy (n = 1). In 12 of 24 (50%) of these patients, relevant findings were detected by a single submodality only: CT (n = 5), PET (n = 7); p for comparison = 0.774). Conclusion:68Ga-DOTATOC-PET/CT influences therapeutic management in about one third of patients examined. CT and PET are comparably sensitive, deliver complementary information and equally contribute to therapeutic decision-making. Thus, despite the merits of the PET modality, the CT component must not be neglected and an optimized multiphase CT protocol is recommended.

Efficacy of Prophylactic Low–Molecular Weight Heparin for Ambulatory Patients With Advanced Pancreatic Cancer: Outcomes From the CONKO-004 Trial

PURPOSE Advanced pancreatic cancer (APC), in addition to its high mortality, accounts for the highest rates of venous thromboembolic events (VTEs). Enoxaparin, a low-molecular weight heparin, is effective in prevention and treatment of VTEs. Some small studies have indicated that this benefit might extend to patients with cancer. PATIENTS AND METHODS Patients with histologically proven APC were randomly assigned to ambulant first-line chemotherapy and prophylactic use of enoxaparin or chemotherapy alone to investigate the probable reduction in symptomatic VTEs and the impact on survival. RESULTS A total of 312 patients were recruited as one of the protocol end points was reached. Within the first 3 months, the numbers of symptomatic VTEs were as follows: 15 of 152 patients in the observation group and two of 160 patients in the enoxaparin group (hazard ratio [HR], 0.12; 95% CI, 0.03 to 0.52; χ(2) P = .001). The numbers of major bleeding events were as follows: five of 152 patients in the observation arm and seven of 160 patients in the enoxaparin arm (HR, 1.4; 95% CI, 0.35 to 3.72; χ(2) P = 1.0). Overall cumulative incidence rates of symptomatic VTEs were 15.1% (observation) and 6.4% (enoxaparin; HR, 0.40; 95% CI, 0.19 to 0.83; P = .01). Progression-free (HR, 1.06; 95% CI, 0.84 to 1.32; P = .64) and overall survival (HR, 1.01; 95% CI, 0.87 to 1.38; P = .44) did not differ between groups. CONCLUSION This study demonstrates the high efficacy and feasibility of primary pharmacologic prevention of symptomatic VTEs in outpatients with APC. Treatment efficacy was not affected by simultaneous treatment with enoxaparin in this trial setting.

Assessment of histological response of paediatric bone sarcomas using FDG PET in comparison to morphological volume measurement and standardized MRI parameters

PurposeThe objective of this study was to evaluate positron emission tomography (PET) using 18F-fluoro-2-deoxy-D-glucose (FDG) in comparison to volumetry and standardized magnetic resonance imaging (MRI) parameters for the assessment of histological response in paediatric bone sarcoma patients.MethodsFDG PET and local MRI were performed in 27 paediatric sarcoma patients [Ewing sarcoma family of tumours (EWS), n = 16; osteosarcoma (OS), n = 11] prior to and after neoadjuvant chemotherapy before local tumour resection. Several parameters for assessment of response of the primary tumour to therapy by FDG PET and MRI were evaluated and compared with histopathological regression of the resected tumour as defined by Salzer-Kuntschik.ResultsFDG PET significantly discriminated responders from non-responders using the standardized uptake value (SUV) reduction and the absolute post-therapeutic SUV (SUV2) in the entire patient population (∆SUV, p = 0.005; SUV2, p = 0.011) as well as in the subgroup of OS patients (∆SUV, p = 0.009; SUV2, p = 0.028), but not in the EWS subgroup. The volume reduction measured by MRI/CT did not significantly discriminate responders from non-responders either in the entire population (p = 0.170) or in both subgroups (EWS, p = 0.950; OS, p = 1.000). The other MRI parameters alone or in combination were unreliable and did not improve the results. Comparing diagnostic parameters of FDG PET and local MRI, metabolic imaging showed high superiority in the subgroup of OS patients, while similar results were observed in the population of EWS.ConclusionFDG PET appears to be a useful tool for non-invasive response assessment in the group of OS patients and is superior to MRI. In EWS patients, however, neither FDG PET nor volumetry or standardized MRI criteria enabled a reliable response assessment to be made after neoadjuvant treatment.

Magnetic resonance imaging including magnetic resonance cholangiopancreatography for tumor localization and therapy planning in malignant hilar obstructions

Purpose: To assess image quality and overall accuracy of magnetic resonance imaging (MRI), including two magnetic cholangiopancreatography (MRCP) techniques, for the diagnostics and preoperative work-up of malignant hilar obstructions. Material and Methods: Thirty-one patients with malignant hilar obstructions (hilar cholangiocarcinoma, n = 30; hepatocellular carcinoma, n = 1) received MRCP by two techniques (single-shot thick-slab and multisection thin-slice MRCP) and unenhanced and contrast material-enhanced MRI. MR assessment included the evaluation of image quality and visualization of bile ducts (5-point scale), and the classification of tumor status. MR results were subsequently correlated with the results from surgery and pathology. Results: The maximum intensity projections of multisection thin-slice MRCP had significantly more artifacts compared to MRCP in the single-shot thick-slab technique, and overall image quality of single-shot thick-slab MRCP was rated significantly superior compared to multisection thin-slice MRCP (4.4±0.7 and 4.1±0.9, respectively). Moreover, ductal visualization of different parts of the biliary system was rated superior with single-shot thick-slab MRCP. In contrast, the original data from multisection thin slice MRCP facilitated visualization of periductal lesions and adjacent structures. Overall MR accuracy for the assessment of tumor status, periductal infiltration, and lymph node metastases was 90%, 87%, and 66%, respectively. Conclusion: For evaluation of malignant hilar obstructions, MRCP by the single-shot thick-slab technique had superior image quality and fewer artifacts; in contrast, besides sole biliary visualization, multisection MRCP depicted complementary adjacent parenchymal and periductal structures. We therefore recommend MRI, with a combination of both MRCP techniques, for the diagnostic work-up and therapy planning of malignant hilar obstructions.

68Ga-DOTATOC PET/CT of Neuroendocrine Tumors: Spotlight on the CT Phases of a Triple-Phase Protocol

The diagnostic value of neuroendocrine tumor (NET) imaging using PET with integrated CT is dependent on both components. This retrospective study assessed the value of the single CT phases of a triple-phase (early arterial, portal-venous inflow, and venous) CT protocol in comparison to 68Ga-DOTATOC PET in a masked reading. Methods: 68Ga-DOTATOC PET/CT examinations from 51 patients with known or suspected NET were included. Two readers assessed the data of PET and each of the 3 CT phases for NET lesions independently (using a 3-point score: 1 = benign, 2 = indeterminate, and 3 = malignant) and by consensus (using binary benign/malignant interpretation only). Only lesions within the field of the abdominal scan were evaluated. Clinical and imaging follow-up, histopathology (if available), and the decision of an interdisciplinary truth-panel served as a standard of reference. In addition to the calculation of standard statistical parameters (including general linear mixed models), interobserver reliability was estimated (Cohens κ). Results: Of 510 abdominal lesions observed, 354 were classified as malignant. Sensitivity was 77.1% for combined triple-phase CT, 53.4% for arterial CT, 66.1% for portal-venous CT, 66.9% for venous CT, and 72.8% for PET. The respective specificities were 85.3%, 92.9%, 92.3%, 89.7%, and 97.4%, and the respective accuracies were 79.6%, 65.5%, 74.1%, 73.9%, and 80.4%. Although arterial CT was found to be inferior to PET, portal-venous CT, and venous CT (P < 0.001), the differences between the other scans were not significant. Detection was exclusively by PET for 16.1% of lesions, by triple-phase CT for 20.3%, by arterial CT for 0.5%, by portal-venous CT for 3.9%, and by venous CT for 3.9%. Regarding interobserver reliability, the κ-value was 0.768 for PET, 0.391 for triple-phase CT, 0.577 for arterial CT, 0.583 for portal-venous CT, and 0.482 for venous CT. Conclusion: No CT phase can be omitted in NET imaging, and the triple-phase protocol continues to be strongly recommended also for PET/CT.

Value of image fusion using single photon emission computed tomography with integrated low dose computed tomography in comparison with a retrospective voxel-based method in neuroendocrine tumours

The objective was the evaluation of single photon emission computed tomography (SPECT) with integrated low dose computed tomography (CT) in comparison with a retrospective fusion of SPECT and high-resolution CT and a side-by-side analysis for lesion localisation in patients with neuroendocrine tumours. Twenty-seven patients were examined by multidetector CT. Additionally, as part of somatostatin receptor scintigraphy (SRS), an integrated SPECT–CT was performed. SPECT and CT data were fused using software with a registration algorithm based on normalised mutual information. The reliability of the topographic assignment of lesions in SPECT–CT, retrospective fusion and side-by-side analysis was evaluated by two blinded readers. Two patients were not enrolled in the final analysis because of misregistrations in the retrospective fusion. Eighty-seven foci were included in the analysis. For the anatomical assignment of foci, SPECT–CT and retrospective fusion revealed overall accuracies of 91 and 94% (side-by-side analysis 86%). The correct identification of foci as lymph node manifestations (n=25) was more accurate by retrospective fusion (88%) than from SPECT–CT images (76%) or by side-by-side analysis (60%). Both modalities of image fusion appear to be well suited for the localisation of SRS foci and are superior to side-by-side analysis of non-fused images especially concerning lymph node manifestations.