Frederik A Verburg

University Hospital RWTH Aachen, Aachen, North Rhine-Westphalia, Germany

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Publications (114)395.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: To compare uptake measurements and different methods for the pretherapeutic determination of the effective thyroidal 131I half life (Teff) to the results of posttherapeutic dosimetric measurements. Patients, methods: Retrospective study of 1538 patients who received their first RIT in our department for autonomous thyroid nodules (ATN), autonomous multinodular goiter (AMG) or Graves' disease (GD) between November 1999 and January 2011. Pretherapeutic measurements were performed at any combination of 24 h, 48 h and 6 days after 131I administration. Post-therapy dosimetric measurements were performed in 12 h intervals until discharge. Teff was determined through monoexponential curve fitting. Results: Pretherapeutic Teff values based on measurements at 24 h and 48 h, 24 h and 6 d, 48 h and 6 d as well as on day 24 h, 48 h and 6 d yielded implausible (< 2 d or > 8 d) values for Teff, in 60.4%, 25.7%, 29.1 and 21.4% of available calculations, respectively. The plausible results showed significant, clinically relevant and sometimes considerable overestimations of Teff. Using empirically determined fixed disease specific Teff values resulted in a better congruence between the pre- and posttherapeutic dosimetry results. 24 h measurements were marginally more accurate than 48 h ones in AMG and GD whereas 48 h measurements were marginally more accurate in ATN; these differences are however not clinically relevant. 6 d measurements are clearly less accurate than those after 24 h or 48 h. Conclusion: In ATN, AMG and GD, pretherapeutic dosimetry can be performed by a single uptake measurement at 24 h or 48 h using a fixed, disease specific value for Teff. Additional later measurements do not yield a further clinically relevant contribution to accuracy of pretherapeutic dosimetry.
    Nuklearmedizin. Nuclear medicine. 12/2014; 54(1).
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    ABSTRACT: The aim of this study is to evaluate the impact of a high resolution (HR) image reconstruction with a voxel size of 2mm in comparison to the most routinely used standard reconstruction with 4mm voxels in patients suffering from prostate cancer having undergone (18)F-methylcholine PET/CT. Phantom studies were performed using a Jaszczak phantom and a custom made phantom containing small hot lesions (size 2-10mm). Clinical evaluation was performed on PET/CT scans of 50 patients. Images were reconstructed with 4mm and 2mm voxel size and analyzed quantitatively using AMIDE and MATLAB. Clinical images were judged by two observers concerning TNM staging, image quality and the correlation of PET and CT data. Phantom studies revealed increased SUVmean and SUVmax values in the HR images (P<0.01). The lower detection limit was approximately 3mm in the HR and 4-5mm in the conventional images. Lower FWHM values were found in the HR images. No significant difference was found concerning the image quality and the correlation of PET and CT (each P>0.5). For both reconstructions, a comparable total amount of lesions was reported (P>0.5) with no impact on the TNM staging. In conclusion, the HR PET reconstruction provides semi-quantitative advantages in the sense of an improved lower detection limit and increased semi-quantitative tumour-to-background ratios. In the setting of choline PET/CT for prostate cancer the high resolution reconstruction could be implemented clinically as there are no relevant qualitative differences between this and the conventional image resolution in terms of image quality, assessment confidence and lesion identification rate.
    Hellenic journal of nuclear medicine 11/2014; · 0.93 Impact Factor
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    ABSTRACT: Abstract Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. The initial treatment consists of total thyroidectomy followed by ablation of thyroid remnants by radioiodine in most cases. As thyroid cells are the only source of thyroglobulin (Tg), circulating Tg serves as a biochemical marker of persistent or recurrent disease in the follow-up of DTC. Due to the suboptimal clinical detection rate of older Tg assays endogenous or exogenous thyrotropin (TSH) stimulations are recommended for unmasking occult disease. However, the development of new Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations, reflecting minimal amounts of thyroid tissue, even without the need for TSH stimulation. Even if the use of these assays still has not found its way in current clinical guidelines, such assays are now increasingly used in clinical practice. As serum Tg measurement is a technically challenging assay and criteria to define a 'highly sensitive' assay may be different, a good knowledge of the technical difficulties and interpretation criteria is of paramount importance for both clinical thyroidologists, laboratory physicians and scientists involved in the care of DTC patients.
    Clinical Chemistry and Laboratory Medicine 10/2014; · 2.96 Impact Factor
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    ABSTRACT: Context: Recent trial results have revived interest in low activity initial I-131 therapy (RIT) of differentiated thyroid cancer (DTC) Objective: compare different initial I-131 activities for outcome. Design: Database study Setting: University hospital Patients: 1298 (698 low risk, 434 high risk M0 and 136 M1) DTC patients, grouped according to ablation activity (I: ≤2000 MBq (54 mCi), II: 2000-3000 MBq (54-81 mCi) and III: >3000 MBq (81 mCi)), subdivided by age (<45 and ≥45 years at diagnosis). Main outcome measures: Complete remission (CR: Tg below functional sensitivity combined with visually negative I-131 diagnostic whole body scintigraphy), recurrence and DTC specific mortality rates, life expectancy. Results: Low risk patients: in patients <45 a lower median cumulative activity was required to achieve CR in group III (3590 MBq) than in groups I (8050 MBq) and II (6300 MBq). In patients ≥45 DTC specific mortality was significantly higher in group I than in groups II and III (15-year:16.1±7.7%, 0.8±0.8% and 7.2±5.5%, respectively; p=0.004). High risk M0 patients: In patients ≥45 the recurrence rate (15-year: 44.4±16.6%, 24.1±7.6% and 8.6±3.9%; p=0.001) and DTC specific mortality (15-year: 51.8±15.8%, 13.2±4.4% and 9.5±3.7%; p=0.004) were significantly higher in group I than in groups II and III. M1 patients: There were no significant differences in survival results between different activity groups in either age category. Conclusion: Before adopting low initial activity RIT for, especially older, low risk patients, results of long-term follow-up should be regarded critically. Low-activity RIT in older high-risk patients is not to be recommended.
    Journal of Clinical Endocrinology &amp Metabolism 09/2014; · 6.31 Impact Factor
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    ABSTRACT: To determine the frequency of seemingly pathological retroperitoneal uptake in the location of the coeliac ganglia in patients undergoing [(68)Ga]PSMA-HBED PET/CT.
    European journal of nuclear medicine and molecular imaging 09/2014; · 5.22 Impact Factor
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    ABSTRACT: Differentiated thyroid cancer is a rare malignancy, but leaves numerous survivors for life-long follow-up. The cornerstone in current guidelines for follow-up is by measuring the thyroid specific tumour marker, thyroglobulin in serum. Most patients can be followed by this method, but some thyroid cancer patients have antithyroglobulin antibodies in serum, both at diagnosis and after treatment, where follow-up is commenced. These antibodies interfere technically in the immunological methods for measuring thyroglobulin, and the antithyroglobulin antibody positive patients are thus eliminated from following current guidelines. In recent years studies have indicated that following the concentration of antithyroglobulin antibodies in serum may be a surrogate marker for recurrence of the thyroid carcinoma. This has recently resulted in publication of an expert position paper, providing a flow scheme for these particular patients. The current review summarises the literature which is the basis for the paper.
    Current Medicinal Chemistry 08/2014; · 3.72 Impact Factor
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    ABSTRACT: To assess the risk of differentiated thyroid cancer (DTC) recurrence, DTC-related mortality and life expectancy in relation to the number of courses of (131)I therapy (RIT) and cumulative (131)I activities required to achieve complete remission (CR).
    European journal of nuclear medicine and molecular imaging 07/2014; · 5.22 Impact Factor
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    ABSTRACT: Context: The determinants of successful I-131 therapy of Graves' disease (GD) are unclear. Objective: To relate dosimetry parameters to outcome of therapy in order to identify significant determinants eu- and/or hypothyroidism after I-131 therapy, in GD patients. Design: Retrospective study. Setting: University hospital. Patients: 206 GD patients treated in our hospital between November of 1999 and January of 2011. All received I-131 therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Main outcome measures: Post-therapy dosimetric thyroid measurements were performed twice daily until discharge; from these measurements thyroid I-131 half-life, the total thyroid absorbed dose and the maximum dose rate after I-131 administration were calculated. Results: 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after I-131 therapy. In univariate analysis non-hyperthyroid and hyperthyroid patients only differed by gender. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal I-131 half life and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (p<0.001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Conclusion: Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.
    Journal of Clinical Endocrinology &amp Metabolism 07/2014; · 6.31 Impact Factor
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    ABSTRACT: A 51-year-old man with a history of metastatic medullary thyroid cancer (MTC) presented with high adrenocorticotropin (ACTH) and urinary free cortisol levels. The diagnosis of ectopic ACTH production, a rare MTC complication, was established in this patient. PET/CT using the somatostatin analogue DOTA-(Tyr)-octreotate labeled with gallium (Ga-DOTATATE) was performed, showing positive radionuclide uptake in multiple MTC metastases. After this therapy with the novel somatostatin analogue, pasireotide was initiated after which urinary free cortisol and ACTH levels decreased. The present case thus illustrates a potential theranostic use of Ga-DOTATATE PET/CT in MTC.
    Clinical Nuclear Medicine 07/2014; · 2.86 Impact Factor
  • Markus Luster, Theresia Weber, Frederik A Verburg
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    ABSTRACT: The concept of individualized therapy is rapidly gaining recognition in the management of patients with differentiated thyroid cancer (DTC). This Review provides an overview of the most important elements of this paradigm shift in DTC management and discusses the implications for clinical practice. In the majority of patients with DTC who have an inherently good prognosis, the extent of surgery, the dosage of (131)I therapy and the use of levothyroxine therapy are all aspects suitable for individualization, on the basis of both the stage of disease and the response to treatment. In individuals with advanced disease, newer imaging techniques, advances in (131)I therapy and the use of targeted molecular therapies (such as multitargeted kinase inhibitors) have provided new options for the personalized care of patients, for whom until recently no effective therapies were available. Individualized therapies could reduce adverse effects, including the sometimes debilitating hypothyroidism that used to be required before initiation of (131)I treatment, and major salivary gland damage, a common and unpleasant side effect of (131)I therapy. Highly individualized interdisciplinary treatment of patients with DTC might lead to improved outcomes with reduced severity and frequency of complications and adverse effects. However, in spite of ongoing research, personalized therapies remain in their infancy.
    Nature Reviews Endocrinology 07/2014; · 12.96 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the changes in the thyroid axis setpoint after long-term suppressive levothyroxine therapy for differentiated thyroid carcinoma and the resulting changes in levothyroxine requirement. Ninety-nine differentiated thyroid cancer patients were reviewed. All patients had at least one known TSH-level≥0.01 mU/l (lower detection limit) and <1.0 mU/l within 2 years of initial treatment (time 1) and had at least one TSH-value≥0.01 mU/l and <1.0 mU/l after continuous LT4 therapy for a minimum of 5 years (time 2).At time 2 the mean LT4 dosage/kg body weight, TSH, FT3, and FT4 levels were significantly lower than at time 1, while body weight was higher. At time 2, the FT3/FT4 ratio rate had dropped significantly (p<0.001). At time 1, patients would require 2.96 μg/kg body weight to reach total TSH suppression. The dose of levothyroxine/kg required for suppression can be lowered by about 0.05 μg/kg body weight for each year of suppressive therapy. After a median of 12.7 years of continuous suppressive levothyroxine therapy, patients would require 2.25 μg/kg body weight (-23.5%) to reach total TSH-suppression. At least part of this reduction was independent of aging. As a result of changes in thyroid hormone metabolism and thyroid axis setpoint, long-term TSH-suppressive therapy contributes to a reduction in the dosage of levothyroxine per kilogram body weight required for full TSH suppression over time.
    Hormone and Metabolic Research 05/2014; 46(11). · 2.04 Impact Factor
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    ABSTRACT: Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up for DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous thyrotropin (TSH) is recommended by current clinical guidelines to detect occult disease with maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation. Use of these highly sensitive Tg assays has not yet been incorporated into clinical guidelines but they will, we believe, be used by physicians caring for patients with DTC. The aim of this clinical position paper is, therefore, to offer advice on the various aspects and implications of using these highly sensitive Tg assays in the clinical care of patients with DTC.
    European Journal of Endocrinology 04/2014; · 3.69 Impact Factor
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    ABSTRACT: Radioiodine scintigraphy influences staging and treatment in patients with differentiated thyroid carcinoma. The limit of detection for fractional uptake in an iodine avid focus in a scintigraphic image was determined from the number of lesion net counts and the count density of the tissue background. The count statistics were used to calculate the diagnostic activity required to elevate the signal from a lesion with a given uptake significantly above a homogeneous background with randomly distributed counts per area. The dependences of the minimal uptake and the minimal size of lesions visible in a scan on several parameters of influence were determined by linking the typical biokinetics observed in iodine avid tissue to the lesion mass and to the absorbed dose received in a radioiodine therapy. The detection limits for fractional uptake in a neck lesion of a typical patient are about 0.001% after therapy with 7000 MBq, 0.01% for activities typically administered in diagnostic assessments (74–185 MBq), and 0.1% after the administration of 10 MBq I-131. Lesions at the limit of detection in a diagnostic scan with biokinetics eligible for radioiodine therapy are small with diameters of a few millimeters. Increasing the diagnostic activity by a factor of 4 reduces the diameter of visible lesions by 25% or about 1 mm. Several other determinants have a comparable or higher influence on the limit of detection than the administered activity; most important are the biokinetics in both blood pool and target tissue and the time of measurement. A generally valid recommendation for the timing of the scan is impossible as the time of the highest probability to detect iodine avid tissue depends on the administered activity as well as on the biokinetics in the lesion and background in the individual patient.
    Physics in Medicine and Biology 04/2014; 59(10):2353. · 2.92 Impact Factor
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    ABSTRACT: To compare the cost-effectiveness of (99m)Tc-methoxyisobutylisonitrile (MIBI) thyroid scintigraphy and the Afirma® gene expression classifier for the assessment of cytologically indeterminate thyroid nodules. A decision tree model was used. Costs were calculated from the perspective of the German health insurance system. The robustness of the results was assessed with probabilistic sensitivity analyses using a Monte Carlo simulation. Life expectancy was 34.3 years (estimated costs per patient 1,459 - 2,224) for the MIBI scan and 34.1 years (estimated costs 3,560 - 4,071) for the molecular test. These results were confirmed by the Monte Carlo simulation. MIBI thyroid scintigraphy is more cost-effective than the gene expression classifier.
    European Journal of Nuclear Medicine 04/2014; 41(8). · 4.53 Impact Factor
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    ABSTRACT: The aim of this study was to assess whether F-FDG PET combined with x-ray CT (F-FDG PET/CT) findings have a prognostic impact in patients with carcinoma of unknown primary (CUP). Seventy patients with CUP who were referred for F-FDG PET/CT were included. F-FDG PET/CT results were checked against available histologic diagnosis and follow-up data. For each patient, the SUVmax of the lesion with maximum uptake was measured. In 26% of the patients, a primary tumor was identified. The follow-up period after F-FDG PET/CT scan ranged between 3 and 45 months. Kaplan-Meier analysis revealed 1-year survival rates of 92% in the group without evidence of malignancy on F-FDG PET/CT, 78% in the group with locoregional disease, and 34% in the group with extensive disease on F-FDG PET/CT. Three-year survival rates in these groups were 73%, 71%, and 23%, respectively (P = 0.001). There was no significant survival difference between patients with regionally confined disease without identification of the primary tumor and those in whom the primary tumor was identified on F-FDG PET/CT (P = 0.25). This was also the case for patients with extensive disease (P = 0.26). The SUVmax of the lesion with maximum uptake was not significantly related to survival (P = 0.56). F-FDG PET/CT is a helpful tool for the identification of the primary tumor in patients with CUP; it is also able to provide an accurate assessment of prognosis based on the extent of the disease without the need for identification of the primary tumor.
    Clinical nuclear medicine 12/2013; · 3.92 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate the diagnostic and prognostic value of combined (18)F-2-fluorodeoxyglucose positron emission tomography and contrast enhanced X-ray computed tomography (FDG-PET/CT) in women with a suspicion of recurrent ovarian cancer. We retrospectively reviewed 48 patients with a suspicion of recurrent ovarian cancer who were referred to our department for combined FDG-PET/CT. Median follow-up was 25 months. 38/48 (79%) patients showed pathological findings on PET/CT. 17/48 (35%) of patients died of ovarian cancer. One FDG-PET/CT was false positive and one was false negative, leading to a sensitivity and positive predictive value of 97% and a specificity and negative predictive value of 90%. 33/48 (69%) underwent a change in therapy following FDG-PET/CT. There was a significantly better survival in FDG-PET/CT negative than in positive patients (p=0.04). In the FDG-PET/CT negative group no patients had died of ovarian cancer during follow-up. Remarkably, there was no difference in survival between patients who only had peritoneal metastases on FDG-PET/CT and those who also had extraperitoneal metastases (p=0.71). A negative FDG-PET/CT has a high negative predictive value for the presence of disease and, more importantly, is associated with a very good disease-specific survival rate.
    European journal of radiology 12/2013; · 2.65 Impact Factor
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    ABSTRACT: In the absence of autoantibodies against thyroglobulin (Tg), Tg measurement nowadays is the cornerstone of clinical management of differentiated thyroid cancer patients. DTC patients presenting with a positive Tg measurement without an anatomical correlate on anatomic imaging provide a management challenge to the attending physician. Based on the literature we will provide an overview of the most important steps to undertake in such patients and their potential clinical consequences.
    Nuklearmedizin 12/2013; 53(1). · 1.67 Impact Factor
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    ABSTRACT: Context:Serum thyroglobulin (Tg) is an indicator of differentiated thyroid cancer (DTC) relapse.Objective:To meta-analyze published data about the diagnostic performance of high-sensitive serum Tg (hsTg) during levothyroxine therapy in DTC follow-up.Data sources:Comprehensive literature search of PubMed/MEDLINE and Scopus for studies published until July 2013Study Selection:Studies investigating the diagnostic performance of basal hsTg in monitoring DTC were eligible. Exclusion criteria were: a) articles not within the field of interest; b) reviews, letters, conference proceedings; c) articles evaluating serum Tg measurement with a functional sensitivity >0.1 ng/ml; d) overlap in patient data; e) insufficient data to reassess diagnostic performance of basal serum hsTg.Data extraction:Information was collected concerning basic study data, patient characteristics and technical aspects. For each study the number of true-positive, false-positive, true-negative and false-negative findings for basal hsTg, considering stimulated Tg measurement as reference standard, were recorded.Data synthesis:Pooled data demonstrated that the negative predictive value (NPV) of hsTg using both assays was 97% and 99% considering a stimulated Tg measurement >1 ng/ml and >2 ng/ml as cut-off for positivity, respectively. Despite the high pooled sensitivity of basal hsTg, the pooled specificity, accuracy and positive predictive value (PPV) were insufficient to completely substitute stimulated Tg measurement.Conclusions:Basal hsTg measurement has a very high NPV but an insufficient PPV for monitoring DTC patients. Therefore, a Tg stimulation test can be avoided in patients with an undetectable basal hsTg whereas a stimulated Tg measurement should be considered when hsTg levels are detectable.
    The Journal of Clinical Endocrinology and Metabolism 11/2013; · 6.31 Impact Factor
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    ABSTRACT: To evaluate the prognostic value of O-(2-[(18)F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organisation (WHO) tumor grade II-IV gliomas. We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40 % of the SUVmax. Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40 % SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality (p = 0.005) and progression-free survival (p = 0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade (p = 0.001) and SUVmax ≥ 2.6 (p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 (p = 0.007) and being treated for a recurrence rather than for a primary tumor manifestation (p = 0.014) were predictors for progression-free survival, but not TBRmax or TBRmean. In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval.
    Annals of Nuclear Medicine 11/2013; · 1.41 Impact Factor
  • European Journal of Nuclear Medicine 11/2013; · 4.53 Impact Factor

Publication Stats

582 Citations
395.13 Total Impact Points


  • 2012–2014
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
  • 2009–2014
    • University of Wuerzburg
      • Department of Nuclear Medicine
      Würzburg, Bavaria, Germany
  • 2011–2013
    • RWTH Aachen University
      • Department of Nuclear Medicine
      Aachen, North Rhine-Westphalia, Germany
  • 2010–2013
    • Ente Ospedaliero Cantonale
      Bellinzona, Ticino, Switzerland
  • 2010–2012
    • Universität Ulm
      • Clinic of Nuclear Medicine
      Ulm, Baden-Wuerttemberg, Germany
  • 2009–2011
    • Department of Nuclear Medicine
      Nyitra, Nitriansky, Slovakia
  • 2009–2010
    • St. Antonius Ziekenhuis
      • Department of Nuclear Medicine
      Nieuwegen, Utrecht, Netherlands
  • 2004–2009
    • University Medical Center Utrecht
      • Department of Image Processing
      Utrecht, Provincie Utrecht, Netherlands