16125
2018
eng
article
1
2018-04-29
--
--
Predictive value of \(^{18}\)F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib
Introduction: Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKI). We
aimed to assess the role of metabolic imaging using 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography/computed tomography (PET/CT) shortly before and 3 months after initiation of TKI treatment.
Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after TKI treatment initiation. During follow-up, CT scans were performed every 3 months and analyzed according to Response Evaluation Criteria In Solid Tumors (RECIST). The predictive value for estimating progression-free (PFS) and overall survival (OS) was examined by investigating \(^{18}\)F-FDG mean/maximum standardized uptake values (SUVmean/max) of the metabolically most active lesion as well as by analyzing clinical parameters (tumor marker doubling times {calcitonin, carcinoembryonic antigen (CEA)}, prior therapies, RET (rearranged during transfection) mutational status, and disease type).
Results: Within a median follow-up of 5.2 years, 9 patients experienced disease progression after a median time interval of 2.1y whereas the remainder had ongoing disease control (n=5 partial response and n=4 stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5y after TKI initiation.
Pre-therapeutic SUVmean >4.0 predicted a significantly shorter PFS (PFS: 1.9y vs. 5.2y; p=0.04). Furthermore, sustained high 18F-FDG uptake at 3 months with a SUVmean>2.8 tended to portend an unfavorable prognosis with a PFS of 1.9y (vs. 3.5y; p=0.3). Prolonged CEA doubling times were significantly correlated with longer PFS (r=0.7) and OS (r=0.76, p<0.01, respectively). None of the other clinical parameters had prognostic significance.
Conclusions: Pre-therapeutic \(^{18}\)F-FDG PET/CT holds prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. Low tumor metabolism of SUVmean < 4.0 prior to treatment predicts longer progression-free survival.
Journal of Nuclear Medicine
10.2967/jnumed.117.199778
0161-5505
https://www.ncbi.nlm.nih.gov/pubmed/29025983
urn:nbn:de:bvb:20-opus-161256
This research was originally published in JNM. Rudolf A. Werner, Jan-Stefan Schmid, Takahiro Higuchi, Mehrbod S. Javadi, Steven P. Rowe, Bruno Märkl, Christoph Aulmann, Martin Fassnacht, Matthias Kroiss, Christoph Reiners, Andreas K. Buck, Michael C. Kreissl, Constantin Lapa. Predictive value of 18F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib. J Nucl Med. May 1, 2018;vol. 59 no. 5: 756-761. © SNMMI.
Johns Hopkins University School of Medicine
Journal of Nuclear Medicine May 1, 2018 vol. 59 no. 5 756-761. doi:10.2967/jnumed.117.199778
701983
Deutsches Urheberrecht
Rudolf Werner
Jan-Stefan Schmid
Takahiro Higuchi
Mehrbod S. Javadi
Steven P. Rowe
Bruno Märkl
Christoph Aulmann
Martin Fassnacht
Matthias Kroiß
Christoph Reiners
Andreas Buck
Michael Kreissl
Constantin Lapa
eng
uncontrolled
positron emission tomography
deu
swd
Medullärer Schilddrüsenkrebs
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
medullary thyroid carcinoma
eng
uncontrolled
tyrosine kinase inhibitor
eng
uncontrolled
vandetanib
eng
uncontrolled
2- deoxy-2-(18F)fluoro-D-glucose
eng
uncontrolled
18F-FDG
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16125/Werner_Rudolf_Vandetanib_JNM_accepted_version.pdf
16791
2018
eng
article
1
2018-09-03
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Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib
Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET.
Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated.
Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.).
Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.
Endocrine
1355-008X
10.1007/s12020-018-1749-3
urn:nbn:de:bvb:20-opus-167910
Johns Hopkins School of Medicine
Endocrine (2018). https://doi.org/10.1007/s12020-018-1749-3
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Ralph A. Bundschuh
Takahiro Higuchi
Mehrbod S. Javadi
Steven P. Rowe
Norbert Zsótér
Matthias Kroiss
Martin Fassnacht
Andreas K. Buck
Michael C. Kreissl
Constantin Lapa
eng
uncontrolled
personalized medicine
deu
swd
Positronen-Emissions-Tomografie
eng
uncontrolled
medullary thyroid carcinoma
eng
uncontrolled
tyrosine kinase inhibitor
eng
uncontrolled
TKI
eng
uncontrolled
vandetanib
eng
uncontrolled
18F-FDG
eng
uncontrolled
positron emission tomography
eng
uncontrolled
2-deoxy-2-(18F)fluoro-D-glucose
eng
uncontrolled
PET
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16791/Rudolf_Werner_VolumetricAndTextureAnalysis_Endocrine_2018.pdf
17176
2018
eng
17631
8
article
1
2018-11-13
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Left Ventricular Diastolic Dysfunction in a Rat Model of Diabetic Cardiomyopathy using ECG-gated \(^{18}\)F-FDG PET
In diabetic cardiomyopathy, left ventricular (LV) diastolic dysfunction is one of the earliest signs of cardiac involvement prior to the definitive development of heart failure (HF). We aimed to explore the LV diastolic function using electrocardiography (ECG)-gated \(^{18}\)F-fluorodeoxyglucose positron emission tomography (\(^{18}\)F-FDG PET) imaging beyond the assessment of cardiac glucose utilization in a diabetic rat model. ECG-gated \(^{18}\)F-FDG PET imaging was performed in a rat model of type 2 diabetes (ZDF fa/fa) and ZL control rats at age of 13 weeks (n=6, respectively). Under hyperinsulinemic-euglycemic clamp to enhance cardiac activity, \(^{18}\)F-FDG was administered and subsequently, list-mode imaging using a dedicated small animal PET system with ECG signal recording was performed. List-mode data were sorted and reconstructed into tomographic images of 16 frames per cardiac cycle. Left ventricular functional parameters (systolic: LV ejection fraction (EF), heart rate (HR) vs. diastolic: peak filling rate (PFR)) were obtained using an automatic ventricular edge detection software. No significant difference in systolic function could be obtained (ZL controls vs. ZDF rats: LVEF, 62.5±4.2 vs. 59.4±4.5%; HR: 331±35 vs. 309±24 bpm; n.s., respectively). On the contrary, ECG-gated PET imaging showed a mild but significant decrease of PFR in the diabetic rats (ZL controls vs. ZDF rats: 12.1±0.8 vs. 10.2±1 Enddiastolic Volume/sec, P<0.01). Investigating a diabetic rat model, ECG-gated \(^{18}\)F-FDG PET imaging detected LV diastolic dysfunction while systolic function was still preserved. This might open avenues for an early detection of HF onset in high-risk type 2 diabetes before cardiac symptoms become apparent.
Scientific Reports
10.1038/s41598-018-35986-0
urn:nbn:de:bvb:20-opus-171765
Scientific Reports 8:17631 (2018). DOI: 10.1038/s41598-018-35986-0
701983
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Rudolf A. Werner
Christoph Eissler
Nobuyuki Hayakawa
Paula Arias-Loza
Hiroshi Wakabayashi
Mehrbod S. Javadi
Xinyu Chen
Tetsuya Shinaji
Constantin Lapa
Theo Pelzer
Takahiro Higuchi
eng
uncontrolled
diabetic cardiomyopathy
eng
uncontrolled
personalized treatment
eng
uncontrolled
precision medicine
eng
uncontrolled
ZDF rats
eng
uncontrolled
ECG
eng
uncontrolled
PET
eng
uncontrolled
\(^{18}\)F-fluorodeoxyglucose
eng
uncontrolled
\(^{18}\)F-FDG
eng
uncontrolled
diabetes
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Medizinische Klinik und Poliklinik I
OpenAIRE
Förderzeitraum 2018
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17176/Werner_Scientific_Reports.pdf