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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA); 20180919-20180922; Wien; DOCP12.5 /20180919/
    Publication Date: 2018-09-20
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 2
    Abstract: BACKGROUND: Previous studies suggested the maximum tumor to background ratio (TBRmax) in FMISO PET images as a potentially predictive parameter for local control after radio-chemotherapy (CRT) in head and neck squamous cell carcinomas (HNSCC). However, different TBRmax thresholds for stratification were reported, implying that a common threshold cannot readily be used among different institutions without the risk of reducing prediction accuracy. Therefore, this study investigated the robustness of using a common pre-defined TBRmax, simulating a multicenter clinical trial. MATERIAL AND METHODS: FMISO PET/CT was performed four hours post-injection in 22 patients with advanced HNSCC in a phase II FMISO dose escalation study. PET background regions of interest (ROIs) were manually defined in deep neck muscles. TBRmax was calculated as the mean of the highest-valued voxels within the high risk RT planning target volume. Its predictive power with respect to local control was tested, classifying patients using median TBRmax as threshold. The influence of systematically varying quantification between institutions was studied in silico by applying offsets of +/- 10% and +/- 20% to the TBRmax of all patients, while the threshold remained constant. The effect was analyzed using a receiver operating characteristic (ROC). True positive and false positive rates (TPR/FPR) as well as positive and negative predictive values (PPV/NPV) were evaluated. RESULTS: For the reference condition without an offset the median TBRmax was 2.0 (1.4-3.5). Patients were classified using this threshold and TPR = 0.7, FPR = 0.4, PPV = 0.5 and NPV = 0.8 were observed. Accuracy declined with increasing offsets. Negative offsets of -10% and -20% resulted in TPR = 0.43 and 0.14, FPR = 0.20 and 0.13, PPV = 0.50 and 0.33 and NPV = 0.75 and 0.68, respectively. Positive offsets of + 10% and + 20% resulted in TPR = 1.00 and 1.00, FPR = 0.53 and 0.67, PPV = 0.47 and 0.41 and NPV = 1.00 and 1.00, respectively. CONCLUSIONS: Using a common pre-defined TBRmax threshold in multicenter trials requires careful standardization and harmonization of all steps from patient preparation to image analysis. Our results indicate that TBRmax should deviate less than 10% from reference conditions (absolute value in this dataset +/- 0.2). This conclusion likely applies to all low contrast nitroimidazole hypoxia PET tracers.
    Type of Publication: Journal article published
    PubMed ID: 26481464
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  • 3
    Abstract: PURPOSE: Prostate-specific membrane antigen (PSMA) is expressed ubiquitously on the membrane of most prostate tumors and its metastasis. While PET/CT using 11C-choline was considered as the gold standard in the staging of prostate cancer, PET with radiolabelled PSMA ligands was introduced into the clinic in recent years. Our aim was to compare the PSMA ligand 68Ga-PSMA-11 with 11C-choline in patients with primary and recurrent prostate cancer. METHODS: 123 patients underwent a whole-body PET/CT examination using 68Ga-PSMA-11 and 11C-choline. Suspicious lesions were evaluated visually and semiquantitatively (SUVavg). Out of these, 103 suffered from a confirmed biochemical relapse after prostatectomy and/or radiotherapy (mean PSA level of 4.5 ng/ml), while 20 patients underwent primary staging. RESULTS: In 67 patients with biochemical relapse, we detected 458 lymph nodes suspicious for metastasis. PET using 68Ga-PSMA-11 showed a significantly higher uptake and detection rate than 11C-choline PET. Also 68Ga-PSMA-11 PET identified significantly more patients with suspicious lymph nodes as well as affected lymph nodes regions especially at low PSA levels. Bone lesions suspicious for prostate cancer metastasis were revealed in 36 patients' biochemical relapse. Significantly more bone lesions were detected by 68Ga-PSMA-11, but only 3 patients had only PSMA-positive bone lesions. Nevertheless, we detected also 29 suspicious lymph nodes and 8 bone lesions, which were only positive as per 11C-choline PET. These findings led to crucial differences in the TNM classification and the identification of oligometastatic patients. In the patients who underwent initial staging, all primary tumors showed uptake of both tracers. Although significantly more suspicious lymph nodes and bone lesions were identified, only 2 patients presented with bone lesions only detected by 68Ga-PSMA-11 PET. CONCLUSION: Thus, PET using 68Ga-PSMA-11 showed a higher detection rate than 11C-choline PET for lymph nodes as well as bone lesions. However, we found lymph nodes and bone lesions which were not concordant applying both tracers.
    Type of Publication: Journal article published
    PubMed ID: 27557844
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  • 4
    Abstract: Differential diagnosis and therapy of heterogeneous breast tumors poses a major clinical challenge. To address the need for a comprehensive, noninvasive strategy to define the molecular and functional profiles of tumors in vivo, we investigated a novel combination of metabolic PET and diffusion-weighted (DW)-MRI in the polyoma virus middle T antigen transgenic mouse model of breast cancer. The implementation of a voxelwise analysis for the clustering of intra- and intertumoral heterogeneity in this model resulted in a multiparametric profile based on [(18)F]Fluorodeoxyglucose ([(18)F]FDG)-PET and DW-MRI, which identified three distinct tumor phenotypes in vivo, including solid acinar, and solid nodular malignancies as well as cystic hyperplasia. To evaluate the feasibility of this approach for clinical use, we examined estrogen receptor-positive and progesterone receptor-positive breast tumors from five patient cases using DW-MRI and [(18)F]FDG-PET in a simultaneous PET/MRI system. The postsurgical in vivo PET/MRI data were correlated to whole-slide histology using the latter traditional diagnostic standard to define phenotype. By this approach, we showed how molecular, structural (microscopic, anatomic), and functional information could be simultaneously obtained noninvasively to identify precancerous and malignant subtypes within heterogeneous tumors. Combined with an automatized analysis, our results suggest that multiparametric molecular and functional imaging may be capable of providing comprehensive tumor profiling for noninvasive cancer diagnostics. Cancer Res; 76(18); 5512-22. (c)2016 AACR.
    Type of Publication: Journal article published
    PubMed ID: 27466286
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  • 5
    Abstract: BACKGROUND AND PURPOSE: To prospectively assess the prognostic value of tumour hypoxia determined by dynamic [18F]Fluoromisonidazole (dynFMISO) PET/CT, and to evaluate both feasibility and toxicity in patients with locally advanced squamous cell carcinomas of the head and neck (LASCCHN) treated with dynFMISO image-guided dose escalation (DE) using dose-painting by contours. PATIENTS AND METHODS: We present a planned interim analysis of a randomized phase II trial. N=25 patients with LASCCHN received baseline dynFMISO PET/CT to derive hypoxic volumes (HV). Patients with tumour hypoxia were randomized into standard radiochemotherapy (stdRT) (70Gy/35 fractions) or DE (77Gy/35 fractions) to the HV. Patients with non-hypoxic tumours were treated with stdRT. Loco-regional control (LRC) in hypoxic patients randomized to stdRT was compared to non-hypoxic patients. Feasibility and toxicity were analysed for patients in the DE arm and compared to stdRT. RESULTS: With a mean follow-up of 27months, LRC in hypoxic patients receiving stdRT (n=10) was significantly worse compared to the non-hypoxic group (n=5) (2y-LRC 44.4% versus 100%, p=0.048). The respective LRC for the DE group (n=10) was 70.0%. Treatment compliance as well as acute and late toxicity did not show significant differences between the DE and the standard dose arms. CONCLUSION: Tumour hypoxia determined by baseline dynFMISO PET/CT is associated with a high risk of local failure in patients with LASCCHN. First data suggest that DE to HV is feasible without excess toxicity.
    Type of Publication: Journal article published
    PubMed ID: 28434798
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  • 6
    Abstract: INTRODUCTION: A previous pattern-of-failure study has suggested that up to 50% of the loco-regional failures (LRF) in head and neck squamous cell carcinoma (HNSCC) occur outside the initial hypoxic volume determined by [(18)F]-fluoromisonidazole-PET ([(18)F]-FMISO-PET). The aim of the present analysis was to correlate spatial patterns of failure with respect to the pretherapeutic dynamic [(18)F]-FMISO-PET/CT in HNSCC after radiochemotherapy (RCT). MATERIAL AND METHODS: Within a running phase 2 trial using [(18)F]-FMISO-PET imaging prior to RCT in HNSCC patients (n = 54), we have observed so far 11 LRF with a minimum follow-up of 12 months. For nine patients, LRF imaging (CT or [(18)F]-FDG-PET/CT) for pattern-of-failure analysis was available. Analysis included the static 4-h hypoxic subvolume (VH) as well as a M-parameter volume (VM), which is derived from modeling of dynamic PET. Deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [(18)F]-FMISO-PET/CT and the planning CT was done to quantify the hypoxic subvolumes compared to the recurrent tumor volume. Moreover, a point-of-origin analysis was performed. RESULTS: A total of five local, two regional and two loco-regional recurrences were detected. After deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [(18)F]-FMISO-PET/CT and the planning CT, a significant overlap of the recurrence volume with [(18)F]-FMISO-positive subvolumes in the initial gross tumor volume (GTV) was observed. Median overlap of 40.2%, range 9.4-100.0%, for VH and 49.0%, range 4.4-96.4%, for VM was calculated. The point-of-origin analysis showed median distances of 0.0 mm, range 0.0-11.3 mm to VH and 8.6 mm, range 0.0-15.5 mm to VM, respectively. CONCLUSIONS: Our data suggest that loco-regional recurrences after RCT originate from the initial GTV (primary tumor and/or lymph node metastases) containing hypoxic subvolumes, which supports the concept of hypoxia imaging-based dose escalation.
    Type of Publication: Journal article published
    PubMed ID: 28891398
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  • 7
    Abstract: BACKGROUND: PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [(18)F]-fluorodeoxyglucose (FDG) and [(18)F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancer patients (HNSCC). MATERIAL AND METHODS: Twenty five HNSCC patients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTVprim) were segmented: a highly FDG-avid volume VFDG, a hypoxic volume on the static FMISO image acquired four hours post tracer injection (VH) and a retention/perfusion volume (VM) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated. RESULTS: Sizes of PET-based volumes and the GTVprim are significantly different (GTVprim〉VFDG〉VH 〉VM; p 〈 .05). VH is covered by VFDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4 mm). Coverage of VM is less pronounced. With respect to VFDG and VH, the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3 mm and 6.3 mm, respectively. For two patients, DTAs were larger than 2 cm. CONCLUSIONS: Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.
    Type of Publication: Journal article published
    PubMed ID: 28849721
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  • 8
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    Keywords: Germany ; COMMON ; CT ; DIAGNOSIS ; FOLLOW-UP ; imaging ; DISEASE ; MORTALITY ; NEW-YORK ; ACCURACY ; computed tomography ; NUCLEAR-MEDICINE ; PATIENT ; REPAIR ; EFFICIENT ; tomography ; COMPUTED-TOMOGRAPHY ; sensitivity ; specificity ; CT ANGIOGRAPHY ; ANGIOGRAPHY ; ARTERY ; nuclear medicine ; DISSECTION ; radiology ; HIGH-RESOLUTION ; THORACIC AORTA ; MORBIDITY ; PRINCIPLES ; NUCLEAR ; USA ; aneurysm ; Aorta ; MEDICINE ; NOV ; medical imaging ; ANEURYSMS ; German ; aortic dissection ; aortic disease ; INTRAMURAL HEMATOMA ; MULTIDETECTOR-ROW CT ; multisclice computed tomography (MSCT)
    Abstract: Aortic disease is associated with high morbidity and mortality and thus require an efficient and accurate diagnostic approach, especially in the acute setting. Multislice computed tomography (MSCT) with the option of high-resolution CT angiography (CTA) has emerged as the standard of reference in diagnosis and follow-up of patients with acquired aortic disease. Aortic dissection is the most common aortic emergency, but it remains undiscovered in up to 38% of cases. Sensitivity and specificity of MSCT in the assessment of aortic dissection are greater than 99%. The sensitivity of CT in the detection of inflammatory changes is 83%; its specificity is almost 100%; and its diagnostic accuracy is ca. 94%. This article outlines state-of-the-art principles in diagnostic CT imaging of acquired aortic disease
    Type of Publication: Journal article published
    PubMed ID: 17938873
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  • 10
    Keywords: brain ; IONIZING-RADIATION ; AGENTS ; Germany ; DIAGNOSIS ; imaging ; DEATH ; DISEASE ; NEW-YORK ; RISK ; RISKS ; RESOLUTION ; SURGERY ; LINES ; NUCLEAR-MEDICINE ; radiation ; TIME ; PATIENT ; CONTRAST ; CONTRAST AGENT ; magnetic resonance ; MAGNETIC-RESONANCE ; TRIAL ; TRIALS ; LINE ; arteries ; HEAD ; ATHEROSCLEROSIS ; NECK ; CEREBRAL ARTERIOVENOUS-MALFORMATIONS ; CONTRAST AGENTS ; magnetic resonance angiography ; DIGITAL-SUBTRACTION-ANGIOGRAPHY ; ANGIOGRAPHY ; ARTERY ; VESSELS ; nuclear medicine ; AGENT ; radiology ; RE ; ENHANCED MR-ANGIOGRAPHY ; STENOSIS ; blood-brain barrier ; ionizing radiation ; MORBIDITY ; NUCLEAR ; IMAGE QUALITY ; technique ; TEMPORAL RESOLUTION ; USA ; BARRIER ; BLOOD-BRAIN-BARRIER ; MEDICINE ; medical imaging ; ARTERY STENOSES ; BENEFITS ; RESONANCE ; German ; STEADY-STATE ; BLOOD-BRAIN ; carotid stenosis ; CAROTID-ARTERY STENOSIS ; DOPPLER SONOGRAPHY ; DUPLEX ULTRASONOGRAPHY ; gadofosveset trisodium ; gadolinium ; INITIAL-EXPERIENCE ; INTRACRANIAL ANEURYSMS ; intracranial vasculature
    Abstract: Stroke, a major cause of death and disability in the developed world, is usually caused by atherosclerosis, most commonly an arterio-occlusive lesion at the carotid bifurcation. Numerous multicentre trials have demonstrated that carotid endarterectomy can reduce the risk of stroke in these patients. However, because of the morbidity of catheter angiography coupled with the risks of surgery, the benefits outweigh the risks of surgery only for those with 〉70% carotid artery stenosis. The gold standard method for assessing the degree of stenosis is catheter-directed cerebral digital subtraction angiography; however, this is associated with a small but substantial stroke risk in addition to inherent risks associated with use of ionizing radiation and nephrotoxic contrast agents. The requirement for alternative imaging techniques that do not contribute to morbidity is ideally met by contrast-enhanced magnetic resonance angiography, which eliminates the need for direct catheterization and therefore eliminates stroke risk associated with a patient work-up. Advances in contrast-enhanced magnetic resonance angiography technology have led to a technique that achieves the goals of high spatial and temporal resolution required for stenosis assessment and streamlining of patients along surgical or medical lines. With the advent of a novel contrast agent, gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany), which has a high relaxivity and an extended imaging time, improved diagnosis of carotid artery stenoses with magnetic resonance angiography can be expected. Gadofosveset trisodium facilitates improved first-pass imaging and also delays steady-state imaging with one injection. Although developed for vascular imaging, gadofosveset trisodium may also allow assessment of brain vascularity, blood-brain barrier breakdown and neurodegenerative disease
    Type of Publication: Journal article published
    PubMed ID: 17650558
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