@article{WernerBundschuhHiguchietal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Higuchi, Takahiro and Javadi, Mehrbod S. and Rowe, Steven P. and Zs{\´o}t{\´e}r, Norbert and Kroiss, Matthias and Fassnacht, Martin and Buck, Andreas K. and Kreissl, Michael C. and Lapa, Constantin},
  title     = {Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib},
  series = {Endocrine},
  journal   = {Endocrine},
  issn      = {1355-008X},
  doi       = {10.1007/s12020-018-1749-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167910},
  year      = {2018},
  abstract  = {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.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerSchmidHiguchietal.2018,
  author    = {Werner, Rudolf and Schmid, Jan-Stefan and Higuchi, Takahiro and Javadi, Mehrbod S. and Rowe, Steven P. and M{\"a}rkl, Bruno and Aulmann, Christoph and Fassnacht, Martin and Kroiß, Matthias and Reiners, Christoph and Buck, Andreas and Kreissl, Michael and Lapa, Constantin},
  title     = {Predictive value of \(^{18}\)F-FDG PET in patients with advanced medullary thyroid carcinoma treated with vandetanib},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.117.199778},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161256},
  year      = {2018},
  abstract  = {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.},
  subject      = {Medull{\"a}rer Schilddr{\"u}senkrebs},
  language  = {en}
}
@inproceedings{WernerHayakawaAriasLozaetal.2017,
  author    = {Werner, Rudolf and Hayakawa, Nobuyuki and Arias-Loza, Paula-Anah and Wakabayashi, Hiroshi and Shinaji, Tetsuya and Lapa, Constantin and Pelzer, Theo and Higuchi, Takahiro},
  title     = {Bildgebung der fr{\"u}hen linksventrikul{\"a}ren Dysfunktion mit ECG-gated F-18-FDG PET in einem Diabetes-Ratten-Modell},
  series = {Nuklearmedizin},
  volume    = {56},
  booktitle = {Nuklearmedizin},
  number    = {2},
  publisher = {Schattauer Verlag},
  issn      = {0029-5566},
  doi       = {10.3413/Nukmed-0880-17-02},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161396},
  pages     = {Abstract Nr.: V119},
  year      = {2017},
  abstract  = {Einleitung: Die linksventrikul{\"a}re diastolische Dysfunktion (LVDD) ist bei Diabetikern noch vor Entwicklung einer klinisch apparenten Herzinsuffizienz eines der ersten Anzeichen einer kardialen Beteiligung. Daher soll in dieser Studie untersucht werden, ob die LVDD mit ECG-gated F-18-FDG PET in einem Diabetes-Rattenmodell dargestellt werden kann. Methodik: Es wurden F-18-FDG PET Scans in einem Typ-2-Diabetes Rattenmodell (ZDF fa/fa, n=6) und in ZL Kontrollen (n=6) vorgenommen (Alter, jeweils 13 Wochen). Unter Hyperinsulinemic-Euglycemic Clamp-Technik wurden 37 MBq 18F-FDG {\"u}ber die Schwanzvene appliziert. 15-35 Minuten nach Tracergabe wurden mittels eines Kleintier-PET-Scanners sowie unter EKG-Ableitung PET Scans angefertigt (16 frames/cardiac cycle). Die linksventrikul{\"a}re Ejektionsfraktion (EF) und die Peak F{\"u}llrate (PFR) wurden mittels einer geeigneten Software (Heart Function View) gemessen, wobei die Software an die Gr{\"o}ße des Rattenherzes angepasst wurde. Ergebnisse: Im Alter von 13 Wochen entwickeln ZDF Diabetes-Ratten eine im Vergleich zu Kontrolltieren eine signifikante myokardiale Hypertrophie, best{\"a}tigt durch post-mortem Analyse des Herzgewichtes (994±78mg vs. 871±44mg in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.01). ECG-gated PET zeigte eine signifikante Abnahme der LV diastolischen PFR (10.4±0.5 vs. 11.8±0.4 EDV/sec in ZDF Diabetes-Ratten vs. ZL Kontrollen, p<0.001), jedoch zeigte sich kein signifikanter Unterschied zwischen LVEF und der Herzfrequenz in den untersuchten ZDF Diabetes-Ratten und Kontrollen (LVEF: 60.0±4.5 vs. 63.7±4.1\%, n.s. und HR: 305±25 vs. 323±24 bpm, n.s.). Schlussfolgerung: Im Diabetes-Ratten-Modell kann unter Verwendung eines ECG-gated FDG-PET Protokolls die diastolische Dysfunktion als Parameter der fr{\"u}hen diabetischen Kardiomyopathie nachgewiesen werden.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {de}
}