Publications (51)248.86 Total impact
-
Article: Prognostic Impact of [18F]Fluorothymidine and [18F]Fluoro-D-Glucose Baseline Uptakes in Patients with Lung Cancer Treated First-Line with Erlotinib.
[show abstract] [hide abstract]
ABSTRACT: 3'-deoxy-3'-[(18)F]fluoro-L-thymidine (FLT) and 2'-deoxy-2'-[(18)F]fluoro-D-glucose (FDG) are used to visualize proliferative and metabolic activity of tumors. In this study we aimed at evaluating the prognostic value of FLT and FDG uptake measured by positron emission tomography (PET) in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. FLT and FDG maximum standardized uptake (SUVmax) values per patient were analyzed in 40 chemotherapy naive patients with advanced NSCLC (stage IV) before treatment with erlotinib. Prior therapy median SUVmax was 6.6 for FDG and 3.0 for FLT, respectively. In univariate analysis, patients with an FDG SUVmax <6.6 had a significantly better overall survival (16.3 months [95% confidence interval [CI] 7.1-25.4 months]) compared to patients with an FDG SUVmax ≥6.6 (3.1 months [95% CI 0.6-5.5 months]) (p<0.001, log rank). Similarly, low FLT uptake (SUVmax <3.0) was associated with significantly longer survival (10.3 months (0-23.3 months, 95% CI) compared to high FLT uptake (3.4 months (0-8.1 months, 95% CI) (p = 0.027). The independent prognostic value of baseline FDG uptake was demonstrated in multivariate analysis (p = 0.05, Cox regression). These data suggest that baseline SUVmax values for both FDG and FLT PET might be further developed as markers for prognostic stratification of patients in advanced NSCLC treated with tyrosine kinase inhibitors (TKI) directed against the epidermal growth factor receptor (EGFR). TRIAL REGISTRATION: Clinicaltrials.gov, Identifier: NCT00568841.PLoS ONE 01/2013; 8(1):e53081. · 4.09 Impact Factor -
Article: Tumor lesion glycolysis and tumor lesion proliferation for response prediction and prognostic differentiation in patients with advanced non-small cell lung cancer treated with erlotinib.
[show abstract] [hide abstract]
ABSTRACT: The aim was to assess the value of tumor lesion glycolysis (TLG) and tumor lesion proliferation (TLP) determined by FDG and 3'-deoxy-3'-F-fluorothymidine (FLT) PET for response prediction and prognostic differentiation in patients with advanced non-small cell lung cancer (NSCLC) treated with erlotinib. FDG-PET and FLT-PET were performed in 30 patients with untreated Stage IV NSCLC before start of therapy, 1 (early) and 6 (late) weeks after erlotinib treatment. Functional tumor volume parameters including TLG in FDG-PET and TLP in FLT-PET were measured in the sum of up to 5 lesions per scan. Metabolic response was assessed using different cutoff values for percentage changes of TLG and TLP. Absolute baseline and residual levels of TLG and TLP were used for dichotomizing the patients into 2 groups. Kaplan-Meier analysis and the log-rank test were performed to analyze the association with progression-free survival (PFS). Patients with a metabolic response measured by early changes of TLP and late changes of TLG and TLP showed a significantly better PFS than metabolically nonresponding patients. A lower cutoff value of 20% or 30% for definition of metabolic response showed better differentiation between metabolically responding and nonresponding patients in cases where the 45% cutoff value revealed no significant results. Furthermore, patients with lower absolute early and late residual TLG and TLP levels had a significantly prolonged PFS. In contrast, absolute baseline TLG and TLP levels showed no significant association with PFS. In patients with advanced NSCLC, percentage changes of TLG and TLP and absolute residual TLG and TLP levels under erlotinib treatment emerged as strong predictive factors for PFS. Our findings indicate that a cutoff value of 20% or 30% for definition of metabolic response measured by percentage changes of TLG and TLP provides suitable results for response prediction, which should be further validated.Clinical nuclear medicine 09/2012; 37(11):1058-64. · 3.92 Impact Factor -
Article: Monitoring reversible and irreversible EGFR inhibition with erlotinib and afatinib in a patient with EGFR-mutated non-small cell lung cancer (NSCLC) using sequential [18F]fluorothymidine (FLT-)PET.
[show abstract] [hide abstract]
ABSTRACT: Non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations benefit from treatment with EGFR-targeted therapy. While first-generation ("reversible") EGFR tyrosine kinase inhibitors (TKIs) are well established in the treatment of these patients, the remarkably lower efficacy of second-generation ("irreversible") EGFR-TKIs after failure of reversible EGFR inhibition is far less understood. Here we describe an EGFR-mutated patient treated sequentially with both reversible (erlotinib) and irreversible (afatinib) EGFR-TKIs monitored by sequential [(18)F]fluorothymidine (FLT-)PET. Our observations confirm the value of molecular imaging for assessment of pharmacodynamics and early prediction of response and relapse in these patients.Lung cancer (Amsterdam, Netherlands) 06/2012; 77(3):617-20. · 3.14 Impact Factor -
Article: Nichtkleinzelliges Bronchialkarzinom
[show abstract] [hide abstract]
ABSTRACT: US-amerikanische Daten belegen, dass die Hinzunahme der Fluordesoxyglucose- Positronenemissionstomographie (FDG-PET) im initialen Staging des nichtkleinzelligen Bronchialkarzinoms (NSCLC) zu einem Stadienshift geführt hat. Dabei wurde ein Stadium III (lokal fortgeschrittenes NSCLC) seltener diagnostiziert, umgekehrt ein Stadium IV (Fernmetastasen) häufiger. Zwei randomisierte Studien aus den Niederlanden und zuletzt aus Dänemark zeigten in gleicher Weise, dass nach einer additiv durchgeführten FDG-PET etwa bei jedem fünften Patienten eine „frustrane“ Thorakotomie vermieden werden kann. Hierunter wurden Thorakotomien verstanden, die binnen Jahresfrist wegen Rezidiv, Fernmetastasen oder Tod ohne anhaltenden Erfolg blieben, bzw. Thorakotomien mit dem unerwarteten Nachweis eines N2-Status. Die Bildgebung bezüglich des mediastinalen Lymphknotenstatus besitzt Grenzen. Sind die Ergebnisse in der Computertomographie und in der FDG-PET konkordant pathologisch, ist die Spezifität begrenzt, und die histopathologische Abklärung bleibt erforderlich, sofern im Fall einer N0- oder N1-Situation ein operativ-kurativer Behandlungsansatz möglich wäre. Neben dem Therapiemonitoring einer Chemotherapie mittels PET ist die frühzeitige Beurteilung des Therapieansprechens auf „targeted therapies“ Gegenstand der Forschung. Als PET-Tracer kommt neben FDG (Glucosemetabolismus) Fluorthymidin (FLT) als In-vivo-Marker der Zellproliferation in Betracht. In Mäusen mit einem NSCLC konnte die FLT-PET die gezielte Inhibiton des epidermalen Wachstumsfaktor-Rezeptors (EGFR) bereits 48 h nach Therapiebeginn zeigen. Umgekehrt verhindert die Resistenzmutation T790M die Bindung des EGFR-Tyrosinkinase-(TK-)Inhibitors Erlotinib an die Adenosintriphosphat-(ATP-)Tasche der EGFR-TK. Solche Resistenzmutationen treten im Verlauf einer Therapie mit einem EGFR-Inhibitor häufig auf und wurden im Tiermodell mittels der FLT-PET erkannt. Diese präklinische Studie ist Grundlage für klinische Studien zur FLT-PET in der Vorhersage des Therapieansprechens auf Erlotinib beim NSCLC. Die radiochemische Forschung konzentriert sich auf PET-Tracer, die – wie die pharmakodynamisch wirksamen TK-Inhibitoren – mit ATP um die Bindung an die Enzymtasche der TK konkurrieren. Dadurch werden Veränderungen auf Ebene der TK-Aktivität sehr sensitiv messbar. Allerdings sind die pharmakokinetischen Eigenschaften der bislang getesten Biomarker für die klinische Anwendung noch nicht ausgereift. Data from the USA have demonstrated that fluorodeoxyglucose positron emission tomography (FDG-PET) in the staging of non-small cell lung cancer (NSCLC) is responsible for stage migration. There was a decline in the number of patients with stage III (locally advanced NSCLC) and an increase in the number of patients with stage IV disease (distant metastases). Two randomized trials from the Netherlands and from Denmark have shown that a futile thoracotomy can be avoided in one out of five patients by use of FDG-PET. Futile thoracotomies were defined as relapse, distant metastases, death from any cause within the 1st year after surgery, or a thoracotomy with the unexpected finding of mediastinal lymph node metastases. Imaging for mediastinal lymph nodes has some limitations. When computed tomography and FDG-PET are both pathologic, the specificity is limited and histopathologic verification is necessary, as far as – in case of N0 or N1 – a curative treatment would be possible. Besides therapy monitoring of chemotherapy early interim PET for response evaluation of targeted therapies is a new field of research. PET tracers are FDG (glucose metabolism) as well as 18F-fluorothymidine (FLT) as an in vivo marker of cell proliferation. In mice with NSCLC, FLT-PET could detect the specific epidermal growth factor receptor (EGFR) inhibition 48 h after the start of therapy. The mutation T790M (resistance factor) prevents the EGFR tyrosine kinase (TK) inhibitor erlotinib from binding to the adenosine triphosphate-(ATP-)binding pocket of the EGFR-TK. This mutation develops frequently in the course of therapy with an EGFR inhibitor, and detection by FLT-PET was possible in the animal model. The animal study was the basis for clinical trials to evaluate FLT-PET in the prediction of response to erlotinib in NSCLC. The radiopharmaceutical research is focused on new PET tracers, which are competitive to ATP for binding to the ATP-binding pocket of the EGFR-TK like the therapeutic TK inhibitors. This principle will allow a very sensitive measurement of the activity of TK. At the moment, the pharmacokinetic characteristic of the tested tracers is not suitable for clinical trials. Schlüsselwörter: Bronchialkarzinom-Positronenemissionstomographie-Fluordesoxyglucose-Fluorthymidin-„Targeted therapy“ Key Words: Lung cancer-Positron emission tomography-Fluorodeoxyglucose-Fluorothymidine-Targeted therapyOnkopipeline 04/2012; 3(2):99-105. -
Article: Predictive value of early and late residual 18F-fluorodeoxyglucose and 18F-fluorothymidine uptake using different SUV measurements in patients with non-small-cell lung cancer treated with erlotinib.
[show abstract] [hide abstract]
ABSTRACT: To evaluate the predictive value of early and late residual (18)F-fluorodeoxyglucose (FDG) and (18)F-fluorothymidine (FLT) uptake using different SUV measurements in PET in patients with advanced non-small-cell lung cancer (NSCLC) treated with erlotinib. We retrospectively reviewed data from 30 patients with untreated stage IV NSCLC who had undergone a combined FDG PET and FLT PET scan at 1 week (early) and 6 weeks (late) after the start of erlotinib treatment. Early and late residual FDG and FLT uptake were measured in up to five lesions per scan with different quantitative standardized uptake values (SUV(max), SUV(2Dpeak), SUV(3Dpeak), SUV(50), SUV(A50), SUV(A41)) and compared with short-term outcome (progression vs. nonprogression after 6 weeks of erlotinib treatment). Receiver-operating characteristics (ROC) curve analysis was used to determine the optimal cut-off value for detecting nonprogression after 6 weeks. Kaplan-Meier analysis and the log-rank test were used to evaluate the association between residual uptake and progression-free survival (PFS). Nonprogression after 6 weeks was associated with a significantly lower early and late residual FDG uptake, measured with different quantitative parameters. In contrast, nonprogression after 6 weeks was not associated with early and late residual FLT uptake. Furthermore, patients with a lower early residual FDG uptake measured in terms of SUV(max) and SUV(2Dpeak) had a significantly prolonged PFS (282 days vs. 118 days; p = 0.022) than patients with higher values. Similarly, lower late residual FDG uptake and early residual FLT uptake measured in terms of SUV(3Dpeak), SUV(A50) and SUV(A41), and late FLT uptake measured in terms of SUV(3Dpeak) and SUV(A50) was associated with an improved PFS. Early and late residual FDG uptake, measured using different quantitative SUV parameters, are predictive factors for short-term outcome in patients with advanced NSCLC treated with erlotinib. Additionally, low residual FDG and FLT uptake early and late in the course of erlotinib treatment is associated with improved PFS.European Journal of Nuclear Medicine 04/2012; 39(7):1117-27. · 4.53 Impact Factor -
Article: Cellular response on Auger- and Beta-emitting nuclides: Human embryonic stem cells (hESC) vs. keratinocytes.
[show abstract] [hide abstract]
ABSTRACT: Purpose: We studied the response of human embryonic stem cells (hESC) to the β-emitter (131)I, which affects the entire cell and to the Auger electron emitter (125)I-deoxyuridine ((125)I-dU), primarily affecting the deoxyribonuleic acid (DNA). The effects were also studied in keratinocytes as a prototype for somatic cells. Methods: HESC (H1) and human keratinocytes (HaCaT, human) were exposed to (125)I-dU (5 × 10(-5) - 5 MBq/ml) and (131)I-iodide (5 × 10(-5) - 12.5 MBq/ml) and apoptosis was measured by DNA-fragmentation. Cell morphology was studied by light microscopy and electron microscopy. Transcriptional profiling was done on the Agilent oligonucleotide microarray platform. Results: Auger-process induced no apoptosis but a strong transcriptional response in hESC. In contrast, HaCaT cells showed a pronounced induction of apoptosis but only a moderate transcriptional response. Transcriptional response of hESC was similar after (125)I-dU and (131)I treatments, whereas HaCaT cells expressed a much more pronounced response to (125)I-dU than to (131)I. A striking radiation-induced down-regulation of pluripotency genes was observed in hESC whereas in keratinocytes the enriched gene annotations were related primarily to apoptosis, cell division and proliferation. Conclusions: Human embryonic stem cells respond to ionizing radiation by (125)I-dU and (131)I in a different way compared to keratinocytes. Transcriptional response and gene expression appear to facilitate an escape from programmed cell death by striking a new path which probably leads to cell differentiation.International Journal of Radiation Biology 04/2012; · 2.28 Impact Factor -
Article: Reduced-intensity chemotherapy and PET-guided radiotherapy in patients with advanced stage Hodgkin's lymphoma (HD15 trial): a randomised, open-label, phase 3 non-inferiority trial.
[show abstract] [hide abstract]
ABSTRACT: The intensity of chemotherapy and need for additional radiotherapy in patients with advanced stage Hodgkin's lymphoma has been unclear. We did a prospective randomised clinical trial comparing two reduced-intensity chemotherapy variants with our previous standard regimen. Chemotherapy was followed by PET-guided radiotherapy. In this parallel group, open-label, multicentre, non-inferiority trial (HD15), 2182 patients with newly diagnosed advanced stage Hodgkin's lymphoma aged 18-60 years were randomly assigned to receive either eight cycles of BEACOPP(escalated) (8×B(esc) group), six cycles of BEACOPP(escalated) (6×B(esc) group), or eight cycles of BEACOPP(14) (8×B(14) group). Randomisation (1:1:1) was done centrally by stratified minimisation. Non-inferiority of the primary endpoint, freedom from treatment failure, was assessed using repeated CIs for the hazard ratio (HR) according to the intention-to-treat principle. Patients with a persistent mass after chemotherapy measuring 2·5 cm or larger and positive on PET scan received additional radiotherapy with 30 Gy; the negative predictive value for tumour recurrence of PET at 12 months was an independent endpoint. This trial is registered with Current Controlled Trials, number ISRCTN32443041. Of the 2182 patients enrolled in the study, 2126 patients were included in the intention-to-treat analysis set, 705 in the 8×B(esc) group, 711 in the 6×B(esc) group, and 710 in the 8×B(14) group. Freedom from treatment failure was sequentially non-inferior for the 6×B(esc) and 8×B(14) groups as compared with 8×B(esc). 5-year freedom from treatment failure rates were 84·4% (97·5% CI 81·0-87·7) for the 8×B(esc) group, 89·3% (86·5-92·1) for 6×B(esc) group, and 85·4% (82·1-88·7) for the 8×B(14) group (97·5% CI for difference between 6×B(esc) and 8×B(esc) was 0·5-9·3). Overall survival in the three groups was 91·9%, 95·3%, and 94·5% respectively, and was significantly better with 6×B(esc) than with 8×B(esc) (97·5% CI 0·2-6·5). The 8×B(esc) group showed a higher mortality (7·5%) than the 6×B(esc) (4·6%) and 8×B(14) (5·2%) groups, mainly due to differences in treatment-related events (2·1%, 0·8%, and 0·8%, respectively) and secondary malignancies (1·8%, 0·7%, and 1·1%, respectively). The negative predictive value for PET at 12 months was 94·1% (95% CI 92·1-96·1); and 225 (11%) of 2126 patients received additional radiotherapy. Treatment with six cycles of BEACOPP(escalated) followed by PET-guided radiotherapy was more effective in terms of freedom from treatment failure and less toxic than eight cycles of the same chemotherapy regimen. Thus, six cycles of BEACOPP(escalated) should be the treatment of choice for advanced stage Hodgkin's lymphoma. PET done after chemotherapy can guide the need for additional radiotherapy in this setting. Deutsche Krebshilfe and the Swiss Federal Government.The Lancet 04/2012; 379(9828):1791-9. · 38.28 Impact Factor -
Article: Mediastinal goiter diagnosed by functional imaging.
[show abstract] [hide abstract]
ABSTRACT: A 63-year-old asymptomatic woman with cured Hodgkin diseases presented for restaging. The chest computed tomography showed a mass at the right side of the upper mediastinum. The benignity and the origin of the tissue were unknown. First, we performed a bronchoscopy-guided biopsy but without success. In the next step, we initiated radionuclide imaging with technetium-99m pertechnetate (Tc-99m) and radioiodine (I-123). Low uptake of Tc-99m and intense accumulation of I-123 after 2 and 24 h to the mediastinal mass suggested that the mass was a mediastinal goiter. Based on iodine uptake and the fact that our patient had no symptoms of tracheal compression, we decide to go for a radioiodine therapy.Libyan Journal of Medicine 01/2012; 7. · 0.18 Impact Factor -
Article: Quantitative analysis of response to treatment with erlotinib in advanced non-small cell lung cancer using 18F-FDG and 3'-deoxy-3'-18F-fluorothymidine PET.
[show abstract] [hide abstract]
ABSTRACT: The purpose of this study was to evaluate the relevance for the prediction of clinical benefit of first-line treatment with erlotinib using different quantitative parameters for PET with both (18)F-FDG and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in patients with advanced non-small cell lung cancer. Data were used from a prospective trial involving patients with untreated stage IV non-small cell lung cancer. (18)F-FDG PET and (18)F-FLT PET were performed before and 1 (early) and 6 (late) weeks after erlotinib treatment. Several quantitative standardized uptake values (SUVs) using different definitions of volumes of interest with varying isocontours (maximum SUV [SUV(max)], 2-dimensional peak SUV [SUV(2Dpeak)], 3-dimensional [3D] peak SUV [SUV(3Dpeak)], 3D isocontour at 50% of the maximum pixel value [SUV(50)], 3D isocontour at 50% adapted for background [SUV(A50)], 3D isocontour at 41% of the maximum pixel value adapted for background [SUV(A41)], 3D isocontour at 70% of the maximum pixel value [SUV(70)], 3D isocontour at 70% adapted for background [SUV(A70)], and relative SUV threshold level [SUV(RTL)]) and metabolically active volume measurements were obtained in the hottest single tumor lesion and in the sum of up to 5 lesions per scan in 30 patients. Metabolic response was defined as a minimum reduction of 30% in each of the different SUVs and as a minimum reduction of 45% in metabolically active volume. Progression-free survival (PFS) was compared between patients with and without metabolic response measured with each of the different parameters, using Kaplan-Meier statistics and a log-rank test. Patients with a metabolic response on early (18)F-FDG PET and (18)F-FLT PET in the hottest single tumor lesion as well as in the sum of up to 5 lesions per scan had a significantly longer PFS, regardless of the method used to calculate SUV. However, the highest significance was obtained for SUV(max), SUV(50), SUV(A50), and SUV(A41.) Patients with a metabolic response measured by SUV(max) and SUV(3Dpeak) on late (18)F-FDG PET in the hottest single tumor lesion had a significantly longer PFS. Furthermore, Kaplan-Meier analyses showed a strong association between PFS and response seen by metabolically active volume, measured either in early (18)F-FLT or in late (18)F-FDG. Early (18)F-FDG PET and (18)F-FLT PET can predict PFS regardless of the method used for SUV calculation. However, SUV(max), SUV(50), SUV(A50), and SUV(A41) measured with (18)F-FDG might be the best robust SUV to use for early response prediction. Metabolically active volume measurement in early (18)F-FLT PET and late (18)F-FDG PET may have an additional predictive value in monitoring response in patients with advanced non-small cell lung cancer treated with erlotinib.Journal of Nuclear Medicine 11/2011; 52(12):1871-7. · 6.38 Impact Factor -
Article: Exhalation of ¹³¹I after radioiodine therapy: measurements in exhaled air.
[show abstract] [hide abstract]
ABSTRACT: A considerable amount of radioiodine is exhaled after radioiodine therapy leading to unwanted radiation exposure through inhalation. This study focused on the concentration of radioactivity exhaled and its chemical nature. Air exhaled by 47 patients receiving (131)I-iodine for different thyroid diseases (toxic goitre n = 26, Graves' disease n = 13, thyroid cancer n = 8) was investigated with a portable constant air-flow sampler. Different chemical iodine species were collected separately (organic, elemental and aerosolic) up to 26 h after administration of the radioiodine capsule. The data approximated to a monoexponential time-activity curve when integrated over 100 h. The radioactivity in the filters was measured with a well counter at defined time points after administration. The radioactivity of (131)I in the exhaled air 1 h after administration ranged from 1 to 100 kBq/m(3). Two parameters (half-life of radioiodine exhalation and time-integrated activity over 100 h) were substantially higher in patients with cancer after near-total thyroidectomy (11.8 ± 2.1 h and 535 ± 140 kBq / m(3), respectively) than in patients with hyperfunctioning thyroid tissue due to toxic adenoma (7.6 ± 2.5 h and 115 ± 27 kBq / m(3), respectively) or Graves' disease (6.4 ± 3.6 h and 113 ± 38 kBq / m(3), respectively). The percentage of radioiodine in the exhaled air in relation to radioiodine administered to the patient was between 80 ppm and 150 ppm. The fraction of organically bound radioiodine (mean value) for all time points after administration was 94-99.9%. This percentage did not depend on the type of thyroid disease. The amount of exhaled radioiodine is small but by no means negligible on the first day after administration. This is the first study to provide experimental evidence on a systematic basis that radioiodine becomes exhalable in vivo, i.e. in the patient. The mechanism of organification of orally administered radioiodine remains to be investigated.European Journal of Nuclear Medicine 08/2011; 38(12):2165-72. · 4.53 Impact Factor -
Article: Early prediction of nonprogression in advanced non-small-cell lung cancer treated with erlotinib by using [(18)F]fluorodeoxyglucose and [(18)F]fluorothymidine positron emission tomography.
[show abstract] [hide abstract]
ABSTRACT: Positron emission tomography (PET) with both 2'-deoxy-2'-[(18)F]fluoro-D-glucose (FDG) and 3'-[(18)F]fluoro-3'-deoxy-L-thymidine (FLT) was evaluated with respect to the accuracy of early prediction of nonprogression following erlotinib therapy, independent from epidermal growth factor receptor (EGFR) mutational status, in patients with previously untreated advanced non-small-cell lung cancer (NSCLC). Thirty-four patients with untreated stage IV NSCLC were evaluated in this phase II trial. Changes in FDG and FLT uptake after 1 (early) and 6 (late) weeks of erlotinib treatment were compared with nonprogression measured by computed tomography after 6 weeks of treatment, progression-free survival (PFS), and overall survival (OS). Changes in FDG uptake after 1 week of therapy predicted nonprogression after 6 weeks of therapy with an area under the receiver operating characteristic curve of 0.75 (P = .02). Furthermore, patients with an early metabolic FDG response (cutoff value: 30% reduction in the peak standardized uptake value) had significantly longer PFS (hazard ratio [HR], 0.23; 95% CI, 0.09 to 0.59; P = .002) and OS (HR, 0.36; 95% CI, 0.13 to 0.96; P = .04). Early FLT response also predicted significantly longer PFS (HR, 0.31; 95% CI, 0.10 to 0.95; P = .04) but not OS and was not predictive for nonprogression after 6 weeks of therapy. Early FDG-PET predicts PFS, OS, and nonprogression after 6 weeks of therapy with erlotinib in unselected, previously untreated patients with advanced NSCLC independent from EGFR mutational status.Journal of Clinical Oncology 03/2011; 29(13):1701-8. · 18.37 Impact Factor -
Article: One should not just read what one believes: the nearly irresolvable issue of producing truly objective, evidence-based guidelines for the management of differentiated thyroid cancer.
European Journal of Nuclear Medicine 01/2011; 38(5):793-8. · 4.53 Impact Factor -
Article: Primary tumour size is a prognostic parameter in patients suffering from differentiated thyroid carcinoma with extrathyroidal growth: results of the MSDS trial.
[show abstract] [hide abstract]
ABSTRACT: The Multicentre Study Differentiated Thyroid Cancer (MSDS) collective represents a well-defined group of patients with thyroid carcinomas with extrathyroidal extension. The aim of the present study was to evaluate the relationship of the primary tumour size with clinicopathological features as well as the outcome of patients with minimum and extensive extrathyroidal growth (pT3b- and pT4a-tumours; UICC 2002/2003, 6th ed). The tumour diameter was available in 324 out of 351 MSDS patients (244 females, 80 males). Mean age of patients was 47.7±12.0 years (range, 20.1-69.8 years), and the median follow-up was 6.2 years. The relationship between primary tumour size and the following clinicopathological data was investigated: age, gender, histological tumour type (papillary thyroid carcinomas (PTC) versus follicular thyroid carcinomas (FTC)) and UICC/AJCC TNM classification. In addition, the correlation between primary tumour size and event-free and overall survival was assessed. The FTC of our series were significantly larger than PTC (3.46 vs 1.84 cm; P<0.001). Patients suffering from pT3b-tumours presented with significantly smaller tumour size than those with extensive extrathyroidal growth (pT4a-tumours) (1.9 vs 3.0 cm; P<0.01). All patients with distant metastases suffered from tumours >2 cm. Furthermore, event-free and overall survival were significantly correlated with increasing tumour size (P<0.05). Using multivariate analysis, a pT4a-category and a tumour diameter >2 cm remained independent predictors of survival. In patients suffering from differentiated thyroid carcinoma with extrathyroidal growth (pT3b and pT4a), the tumour size is an independent predictor of event-free and overall survival.European Journal of Endocrinology 10/2010; 163(4):637-44. · 3.42 Impact Factor -
Article: The role of PET in Hodgkin's lymphoma and its impact on radiation oncology.
[show abstract] [hide abstract]
ABSTRACT: A high negative-predictive value of (18)F-fluorodeoxyglucose (FDG) PET in early and late response assessment of Hodgkin's lymphoma patients has been observed in numerous trials. The consequent substantial reduction in the number of chemotherapy cycles and radiotherapy in many current trials seems to be very promising. The criteria used to describe (18)F-FDG accumulation are widely standardized, but PET interpretation in a dedicated clinical algorithm is being discussed among study groups and will be evaluated in the ongoing trials. The integration of (18)F-FDG PET into radiation treatment planning could have a substantial impact on treatment volumes within the new target definition 'involved-node radiotherapy'. Involved-node radiotherapy has been proposed as a means to further improve the therapeutic ratio by reducing the risk of acute radiation-induced toxicity and potentially lowering the rate of long-term complications, including secondary malignancies.Expert Review of Anti-infective Therapy 09/2010; 10(9):1419-28. · 2.65 Impact Factor -
Article: The role of PET in Hodgkin''s lymphoma and its impact on radiation oncology
[show abstract] [hide abstract]
ABSTRACT: A high negative-predictive value of 18F-fluorodeoxyglucose (FDG) PET in early and late response assessment of Hodgkin''s lymphoma patients has been observed in numerous trials. The consequent substantial reduction in the number of chemotherapy cycles and radiotherapy in many current trials seems to be very promising. The criteria used to describe 18F-FDG accumulation are widely standardized, but PET interpretation in a dedicated clinical algorithm is being discussed among study groups and will be evaluated in the ongoing trials. The integration of 18F-FDG PET into radiation treatment planning could have a substantial impact on treatment volumes within the new target definition ``involved-node radiotherapy''. Involved-node radiotherapy has been proposed as a means to further improve the therapeutic ratio by reducing the risk of acute radiation-induced toxicity and potentially lowering the rate of long-term complications, including secondary malignancies.Expert Review of Anti-infective Therapy 08/2010; 10(9):1419-1428. · 2.65 Impact Factor -
Article: Interpretation and validation of interim positron emission tomography in Hodgkin lymphoma.
Leukemia & lymphoma 03/2010; 51(3):552-3. · 2.40 Impact Factor -
Article: Development of anti-CD30 radioimmunoconstructs (RICs) for treatment of Hodgkin's lymphoma. Studies with cell lines and animal studies.
[show abstract] [hide abstract]
ABSTRACT: Comparison of the binding affinity to a CD30-positive Hodgkin lymphoma (HL) cell line and biodistribution in HL bearing mice of new anti-CD30 radioimmunoconjugates (RICs) of varying structure and labelling nuclides. The antibodies Ki-4 and 5F11 were radioiodinated by the chloramine T method or labelled with (111)In via p-NCS-Benzyl-DOTA. In addition, the Ki-4-dimer was investigated in the iodinated form. The RICs were analyzed for retained immunoreactivity by immunochromatography. In-vitro binding studies were performed on CD30-positive L540 cell lines. For in-vivo biodistribution studies, SCID mice bearing human HL xenografts were injected with the various radioimmunoconjugates. After 24 h, activities in the organs and tumour were measured for all 5 RICs. Tumour-free animals were studied in the same way with (131)I- Ki-4 24 h p. i. The three RICs with the highest tumour/background ratios 24 h p.i. ((131)I-Ki-4, (131)I-5F11, (111)In-bz-DOTA-Ki-4) were analysed further at 48 h and 72 h. All the RICs were successfully labelled with high specific activities (28-47 TBq/mmol) and sufficient radiochemical yields (>80%). Scatchard plot analysis proved high tumour affinity (KD = 20-220 nmol/l). In-vivo tumour accumulation in % of injected dose per g tissue (%ID/g) lay between 2.6 ((131)I-5F11) and 12.3 % ID/g ((131)I-Ki-4) with permanently high background in blood. Tumour/blood-ratios of all RICs were below one at all time points. In-vitro tumour cell affinities of all RICs were promising. However, in-vivo biokinetics tested in the mouse model did not meet expectations. This highlights the importance of developing and testing further new anti-CD30 conjugates.Nuklearmedizin 01/2010; 49(3):97-105. · 1.28 Impact Factor -
Article: [18F]-Fluorodeoxyglucose-positron emission tomography for the assessment of histopathologic response and prognosis after completion of neoadjuvant chemoradiation in esophageal cancer.
[show abstract] [hide abstract]
ABSTRACT: To evaluate the potential of [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) after the completion of neoadjuvant chemoradiation for the assessment of histopathologic response and prognosis in the multimodality treatment of patients with esophageal cancer. Combined chemoradiation with and without surgery are widely accepted treatment options for patients with locally advanced esophageal cancer. Evidence suggests that patients with response to chemoradiation have no additional benefit from surgery compared with definitive chemoradiation. However, there is still a great lack in noninvasive markers for response assessment in patients with esophageal cancer undergoing multimodality treatment. Interestingly, recent studies imply that FDG-PET significantly correlates with histopathologic response and survival in patients with esophageal cancer undergoing neoadjuvant chemotherapy followed by surgical resection. Study patients were recruited from a prospective clinical observation trial on neoadjuvant chemoradiation for esophageal cancer between 1997 and 2006. The study included 119 (98 men, 21 women; median age, 59.4 years; squamous cell cancer: 66; adenocarcinoma: 53) patients with locally advanced esophageal cancer (cT2- 4, N(x), M(0)). All patients received neoadjuvant chemoradiation (cisplatin, 5-FU, 36 Gy) and subsequently underwent transthoracic en bloc esophagectomy. Histomorphologic regression was defined as major histopathologic response when resected specimens contained less than 10% vital residual tumor cells (major response: 47 patients [39.5%]; minor response: 72 patients [60.5%]). FDG-PET was performed before and 2 to 3 weeks after the end of chemoradiation with assessment of the intratumoral FDG-uptake (pretreatment standardized uptake value; post-treatment standardized uptake value; percentage change). These variables were correlated with histopathologic response and survival. Major histomorphologic response was confirmed as an important prognostic factor (P = 0.005; log-rank test). Neoadjuvant chemoradiation led to a significant reduction of intratumoral FDG-uptake (P = 0.0001). A nonsignificant association was seen between major responders and FDG-PET results (P = 0.056). However, the receiver operating characteristic analysis could not identify a standardized uptake value threshold with a relevant predictive value for histomorphologic response. No significant association between metabolic imaging and prognosis was found. FDG-PET seems not to be an imaging system that effectively characterizes the groups of major and minor response as well as survival in patients with esophageal cancer after multimodality treatment.Annals of surgery 12/2009; 250(6):888-94. · 7.90 Impact Factor -
Article: Downregulation of 18F-FDG uptake in PET as an early pharmacodynamic effect in treatment of non-small cell lung cancer with the mTOR inhibitor everolimus.
[show abstract] [hide abstract]
ABSTRACT: Everolimus downregulates glucose metabolism-associated genes in preclinical models. Inhibition of glucose metabolism measured by (18)F-FDG PET was postulated to serve as a pharmacodynamic marker in everolimus-treated non-small cell lung cancer (NSCLC) patients. In 8 NSCLC patients treated with everolimus, the percentage change in (18)F-FDG PET uptake (days 8 and 28 relative to baseline) was determined using a variety of summed standardized uptake value (SUV) measures. Both maximum and mean SUVs were used, with normalizations to body surface area and body weight and with and without correcting for plasma glucose levels. In 5 patients, a reduction of (18)F-FDG PET uptake on day 8 was observed with all methods, ranging from -12.8% to -72.2%. These observations demonstrate that inhibition of glucose metabolism is an early effect of everolimus treatment in NSCLC patients and can be assessed using (18)F-FDG PET.Journal of Nuclear Medicine 11/2009; 50(11):1815-9. · 6.38 Impact Factor -
Article: Radioiodine therapy of benign thyroid disorders: what are the effective thyroidal half-life and uptake of 131I?
[show abstract] [hide abstract]
ABSTRACT: The use of radioiodine therapy is common in the treatment of benign thyroid disease. Council directive Euratom 97/43 requires that for all medical exposure of individuals for radiotherapeutic purposes exposures of target volumes should be individually planned. There are several strategies to accomplish this aim for radioiodine therapy including individual radioiodine uptake measurement and using either individual or mean effective radioiodine uptake and half-life. Although it is always simple to use standard activities, the effective thyroidal half-life and thyroidal uptake of I needs to be estimated individually to achieve optimal dosimetric results. We analyzed the radioiodine half-life and uptake in a large number of patients for use in a semi-individual calculation. Patients presenting consecutively between 1 January 2006 and 31 December 2007 were included in the study. Inclusion criteria were the control of hyperthyroidism and withdrawal of antithyroid drugs 2 days before preliminary radioiodine testing and therapy. Patients were treated for Graves' disease (n=363), nontoxic goitre (n=50), toxic goitre (n=639), or toxic uninodular adenoma (n=365). The effective half-life and uptake of I were estimated by uptake measurements after 24 h and 5 days during the preliminary radioiodine test, and serial measurements over 5 days during therapy. The mean effective half-life of I measured during radioiodine therapy was 5.4 days in Graves' disease, 6.4 days in nontoxic goitre, 6.6 days in toxic goitre, and 5.7 days in toxic uninodular adenoma. The mean maximal uptake of I measured during radioiodine therapy was 64% in Graves' disease, 42% in nontoxic goitre, 38% in toxic goitre, and 31% in toxic uninodular adenoma. These actual values analyzed here might be used for a semi-individual calculation of therapeutic activity when an individual approach is not possible.Nuclear Medicine Communications 11/2009; 31(3):201-5. · 1.40 Impact Factor
Top co-authors
Top Journals
Institutions
-
1999–2013
-
Universität Köln
- Department of Nuclear Medicine
Köln, North Rhine-Westphalia, Germany
-
