16791
2018
eng
article
1
2018-09-03
--
--
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
16560
2018
eng
1-8
article
1
2018-07-24
--
--
Longitudinal \(^{18}\)F-FDG PET imaging in a Rat Model of Autoimmune Myocarditis
Aims: Although mortality rate is very high, diagnosis of acute myocarditis remains challenging with conventional tests. We aimed to elucidate the potential role of longitudinal 2-Deoxy-2-\(^{18}\)F-fluoro-D-glucose (\(^{18}\)F-FDG) positron emission tomography (PET) inflammation monitoring in a rat model of experimental autoimmune myocarditis.
Methods and results: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund’s adjuvant. Time course of disease was assessed by longitudinal \(^{18}\)F-FDG PET imaging. A correlative analysis between in- and ex vivo \(^{18}\)F-FDG signalling and macrophage infiltration using CD68 staining was conducted. Finally, immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was performed at different disease stages determined by longitudinal \(^{18}\)F-FDG PET imaging. After immunization, myocarditis rats revealed a temporal increase in 18F-FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter. Localization of CD68 positive cells was well correlated with in vivo \(^{18}\)F-FDG PET signalling (R\(^2\) = 0.92) as well as with ex vivo 18F-FDG autoradiography (R\(^2\) = 0.9, P < 0.001, respectively). CD44 positivity was primarily observed at tissue samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34-positive staining areas were predominantly identified in samples harvested at both sub-acute and chronic phases (i.e. at \(^{18}\)F-FDG decrease).
Conclusion: \(^{18}\)F-FDG PET imaging can provide non-invasive serial monitoring of cardiac inflammation in a rat model of acute myocarditis.
European Heart Journal Cardiovascular Imaging
2047-2404
10.1093/ehjci/jey119
urn:nbn:de:bvb:20-opus-165601
Johns Hopkins School of Medicine
701983
European Heart Journal - Cardiovascular Imaging (2018) 0, 1–8 doi:10.1093/ehjci/jey119
CC BY-NC: Creative-Commons-Lizenz: Namensnennung, Nicht kommerziell 4.0 International
Rudolf Werner
Hiroshi Wakabayashi
Jochen Bauer
Claudia Schütz
Christina Zechmeister
Nobuyuki Hayakawa
Mehrbod S. Javadi
Constantin Lapa
Roland Jahns
Süleyman Ergün
Valerie Jahns
Takahiro Higuchi
eng
uncontrolled
positron emission tomography
deu
swd
Myokarditis
eng
uncontrolled
myocarditis
eng
uncontrolled
inflammation
eng
uncontrolled
18F-FDG
eng
uncontrolled
PET
eng
uncontrolled
personalized treatment
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für Pharmakologie und Toxikologie
Institut für Anatomie und Zellbiologie
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16560/Werner_EHJ_Cardiovascular_Imaging_2018.pdf
16114
2017
eng
169
no. supplement 1
58
conferenceobject
1
2018-04-25
--
--
Predictive value of FDG-PET in patients with advanced medullary thyroid cancer undergoing vandetanib treatment
Introduction: The prognosis of medullary thyroid carcinoma (MTC) is poor using common chemotherapeutic approaches. However, during the last years encouraging results of recently introduced tyrosine kinase inhibitors (TKI) such as vandetanib have been published. In this study we aimed to correlate the results of \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG) positron emission tomography (PET) imaging with treatment outcome.
Methods: Eighteen patients after thyroidectomy with recurrent/advanced MTC lesions receiving vandetanib (300 mg orally/day) could be analysed. A baseline \(^{18}\)F-FDG PET prior to and a follow-up \(^{18}\)F-FDG PET 3 months after TKI initiation were performed. During follow-up, tumor progression was assessed every 3 months including computed tomography according to RECIST. Progression-free survival (PFS) was correlated with the maximum standardized uptake value of \(^{18}\)F-FDG in lymph nodes (SUV(LN)max) or visceral metastases (SUV(MTS)max) as well as with clinical parameters using ROC analysis.
Results: Within median 3.6 years of follow-up, 9 patients showed disease progression at median 8.5 months after TKI initiation. An elevated glucose consumption assessed by baseline \(^{18}\)F-FDG PET (SUV(LN)max > 7.25) could predict a shorter PFS (2 y) with an accuracy of 76.5% (SUV(LN)max <7.25, 4.3 y; p=0.03). Accordingly, preserved tumor metabolism in the follow-up PET (SUV(MTS)max >2.7) also demonstrated an unfavorable prognosis (accuracy, 85.7%). On the other hand, none of the clinical parameters reached significance in response prediction.
Conclusions: In patients with advanced and progressive MTC, tumors with higher metabolic activity at baseline are more aggressive and more prone to progression as reflected by a shorter PFS; they should be monitored more closely. Preserved glucose consumption 3 months after treatment initiation was also related to poorer prognosis.
Journal of Nuclear Medicine
0161-5505
http://jnm.snmjournals.org/content/58/supplement_1/169
urn:nbn:de:bvb:20-opus-161147
This research was originally published in JNM.
Rudolf A. Werner, Takahiro Higuchi, Dirk O. Muegge, Mehrbod S. Javadi, B. Märkl, C. Aulmann, Andreas K. Buck, Martin Fassnacht, Constantin Lapa, Michael C. Kreissl.
Predictive value of FDG-PET in patients with advanced medullary thyroid cancer undergoing vandetanib treatment. J Nucl Med. May 1, 2017; vol. 58 no. supplement 1:169. © SNMMI.
Johns Hopkins School of Medicine, Baltimore, MD, U.S.
Hospital Augsburg, Augsburg, Germany
Journal of Nuclear Medicine May 1, 2017 vol. 58 no. supplement 1 169
701983
Deutsches Urheberrecht
Rudolf Werner
Takahiro Higuchi
Dirk Muegge
Mehrbod S. Javadi
Bruno Märkl
Christoph Aulmann
Andreas K. Buck
Martin Fassnacht
Constantin Lapa
Michael C. Kreissl
eng
uncontrolled
18F-FDG
eng
uncontrolled
vandetanib
eng
uncontrolled
TKI
eng
uncontrolled
PET
eng
uncontrolled
positron emission tomography
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/16114/Werner_Rudolf_Vandetanib_Kongressbeitrag_accepted_version.pdf
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
16112
2017
eng
i1-i3
Supplement
18
conferenceobject
Oxford University Press
1
2018-04-25
--
--
PET-Guided Histological Characterization of Myocardial Infiltrating Cells in a Rat Model of Myocarditis
No abstract available.
European Heart Journal - Cardiovascular Imaging
2047-2404
10.1093/ehjci/jex071
urn:nbn:de:bvb:20-opus-161127
This is a pre-copyedited, author-produced version of an article accepted for publication in European Heart Journal Cardiovascular Imaging following peer review. The version of record . Eur Heart J Cardiovasc Imaging. ISSN: 2047-2404. Supplement, vol. 18, i1-i3, May 2017 is available online at: 10.1093/ehjci/jex071.
European Heart Journal - Cardiovascular Imaging, Volume 18, Issue suppl_1, May 2017, Pages i1–i3, https://doi.org/10.1093/ehjci/jex071
701983
Johns Hopkins School of Medicine, Baltimore, MD, U.S.
Deutsches Urheberrecht
Rudolf Werner
Hiroshi Wakabayashi
Roland Jahns
Süleyman Ergün
Valerie Jahns
Takahiro Higuchi
deu
swd
Myokarditis
eng
uncontrolled
positron emission tomography
eng
uncontrolled
myocarditis
eng
uncontrolled
PET
eng
uncontrolled
18F-FDG
Medizin und Gesundheit
open_access
Klinik und Poliklinik für Nuklearmedizin
Institut für Pharmakologie und Toxikologie
Institut für Anatomie und Zellbiologie
Medizinische Klinik und Poliklinik I
OpenAIRE
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/16112/Werner_Rudolf_Myocarditis.pdf