TY - JOUR A1 - Werner, Rudolf A1 - Schmid, Jan-Stefan A1 - Higuchi, Takahiro A1 - Javadi, Mehrbod S. A1 - Rowe, Steven P. A1 - Märkl, Bruno A1 - Aulmann, Christoph A1 - Fassnacht, Martin A1 - Kroiß, Matthias A1 - Reiners, Christoph A1 - Buck, Andreas A1 - Kreissl, Michael A1 - Lapa, Constantin T1 - Predictive value of \(^{18}\)F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib JF - Journal of Nuclear Medicine N2 - 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. KW - positron emission tomography KW - Medullärer Schilddrüsenkrebs KW - Positronen-Emissions-Tomografie KW - medullary thyroid carcinoma KW - tyrosine kinase inhibitor KW - vandetanib KW - 2- deoxy-2-(18F)fluoro-D-glucose KW - 18F-FDG Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161256 SN - 0161-5505 N1 - 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. ER - TY - CHAP A1 - Werner, Rudolf A1 - Higuchi, Takahiro A1 - Muegge, Dirk A1 - Javadi, Mehrbod S. A1 - Märkl, Bruno A1 - Aulmann, Christoph A1 - Buck, Andreas K. A1 - Fassnacht, Martin A1 - Lapa, Constantin A1 - Kreissl, Michael C. T1 - Predictive value of FDG-PET in patients with advanced medullary thyroid cancer undergoing vandetanib treatment T2 - Journal of Nuclear Medicine N2 - 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. KW - 18F-FDG KW - vandetanib KW - TKI KW - PET KW - positron emission tomography Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161147 UR - http://jnm.snmjournals.org/content/58/supplement_1/169 SN - 0161-5505 N1 - 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. VL - 58 IS - no. supplement 1 ER - TY - JOUR A1 - Geiger, Julia A1 - Hirtler, Daniel A1 - Gottfried, Kristina A1 - Rahman, Ozair A1 - Bollache, Emilie A1 - Barker, Alex J. A1 - Markl, Michael A1 - Stiller, Brigitte T1 - Longitudinal Evaluation of Aortic Hemodynamics in Marfan Syndrome: New Insights from a 4D Flow Cardiovascular Magnetic Resonance Multi-Year Follow-Up Study JF - Journal of Cardiovascular Magnetic Resonance N2 - Background The aim of this 4D flow cardiovascular magnetic resonance (CMR) follow-up study was to investigate longitudinal changes in aortic hemodynamics in adolescent patients with Marfan syndrome (MFS). Methods 4D flow CMR for the assessment of in-vivo 3D blood flow with full coverage of the thoracic aorta was performed twice (baseline scan t1/follow-up scan t2) in 19 adolescent MFS patients (age at t1: 12.7 ± 3.6 years, t2: 16.2 ± 4.3 years) with a mean follow-up duration of 3.5 ± 1.2 years. Ten healthy volunteers (24 ± 3.8 years) served as a control group. Data analysis included aortic blood flow visualization by color-coded 3D pathlines, and grading of flow patterns (helices/vortices) on a 3-point scale (none, moderate, severe; blinded reading, 2 observers). Regional aortic peak systolic velocities and systolic 3D wall shear stress (WSS) along the entire aortic wall were quantified. Z-Scores of the aortic root and proximal descending aorta (DAo) were assessed. Results Regional systolic WSS was stable over the follow-up duration, except for a significant decrease in the proximal inner DAo segment (p = 0.02) between t1 and t2. MFS patients revealed significant lower mean systolic WSS in the proximal inner DAo compared with volunteers (0.78 ± 0.15 N/m\(^{2}\)) at baseline t1 (0.60 ± 0.18 N/m\(^{2}\); p = 0.01) and follow-up t2 (0.55 ± 0.16 N/m\(^{2}\); p = 0.001). There were significant relationships (p < 0.01) between the segmental WSS in the proximal inner DAo, DAo Z-scores (r = −0.64) and helix/vortex pattern grading (r = −0.55) at both t1 and t2. The interobserver agreement for secondary flow patterns assessment was excellent (Cohen’s k = 0.71). Conclusions MFS patients have lower segmental WSS in the inner proximal DAo segment which correlates with increased localized aberrant vortex/helix flow patterns and an enlarged diameter at one of the most critical sites for aortic dissection. General aortic hemodynamics are stable but these subtle localized DAo changes are already present at young age and tend to be more pronounced in the course of time. KW - Marfan syndrome KW - wall shear stress KW - hemodynamics KW - 4D flow cardiovascular magnetic resonance KW - follow-up KW - aorta Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171119 VL - 19 IS - 33 ER -