Rudolf A Werner1,2, Jan-Stefan Schmid1, Takahiro Higuchi1,3, Mehrbod S Javadi2, Steven P Rowe2, Bruno Märkl4, Christoph Aulmann5, Martin Fassnacht6,7, Matthias Kroiss6,7, Christoph Reiners1, Andreas K Buck1, Michael C Kreissl8,9, Constantin Lapa10. 1. Department of Nuclear Medicine, University Hospital, University of Würzburg, Würzburg, Germany. 2. Division of Nuclear Medicine and Molecular Imaging, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland. 3. Department of Bio-Medical Imaging, National Cardiovascular and Cerebral Research Center, Osaka, Japan. 4. Institute for Pathology, Hospital Augsburg, Augsburg, Germany. 5. Medical Department II, Hospital Augsburg, Augsburg, Germany. 6. Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany. 7. Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany. 8. Department of Nuclear Medicine, Hospital Augsburg, Augsburg, Germany; and. 9. Department of Radiology and Nuclear Medicine, University Hospital Magdeburg, Magdeburg, Germany. 10. Department of Nuclear Medicine, University Hospital, University of Würzburg, Würzburg, Germany lapa_c@ukw.de.
Abstract
Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKIs). We aimed to assess the role of metabolic imaging using 18F-FDG PET/CT shortly before and 3 mo after initiation of TKI treatment. Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline 18F-FDG PET/CT before and 3 mo after TKI treatment initiation. During follow-up, CT scans were obtained every 3 mo and analyzed according to RECIST. The predictive value for estimating progression-free survival (PFS) and overall survival (OS) was examined by investigating the 18F-FDG SUVmean/max of the metabolically most active lesion, as well as by analyzing clinical parameters (tumor marker doubling times [calcitonin, carcinoembryonic antigen], prior therapies, rearranged-during-transfection mutational status, and disease type). Results: Within a median follow-up of 5.2 y, 9 patients experienced disease progression after a median interval of 2.1 y, whereas the remainder had ongoing disease control (5 with a partial response and 4 with stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5 y after TKI initiation. A pretherapeutic SUVmean of more than 4.0 predicted a significantly shorter PFS (1.9 y vs. 5.2 y, P = 0.04). Furthermore, sustained high 18F-FDG uptake at 3 mo with a SUVmean of more than 2.8 tended to portend an unfavorable prognosis, with a PFS of 1.9 y (vs. 3.5 y, P = 0.3). Prolonged carcinoembryonic antigen doubling times were significantly correlated with longer PFS (r = 0.7) and OS (r = 0.76, P < 0.01). None of the other clinical parameters had prognostic significance. Conclusion: Pretherapeutic 18F-FDG PET/CT provides prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. A low tumor metabolism with an SUVmean of less than 4.0 before treatment predicts a longer PFS.
Therapeutic options in advanced medullary thyroid carcinoma (MTC) have markedly improved since the introduction of tyrosine kinase inhibitors (TKIs). We aimed to assess the role of metabolic imaging using 18F-FDG PET/CT shortly before and 3 mo after initiation of TKI treatment. Methods: Eighteen patients with advanced and progressive MTC scheduled for vandetanib treatment underwent baseline 18F-FDG PET/CT before and 3 mo after TKI treatment initiation. During follow-up, CT scans were obtained every 3 mo and analyzed according to RECIST. The predictive value for estimating progression-free survival (PFS) and overall survival (OS) was examined by investigating the 18F-FDG SUVmean/max of the metabolically most active lesion, as well as by analyzing clinical parameters (tumor marker doubling times [calcitonin, carcinoembryonic antigen], prior therapies, rearranged-during-transfection mutational status, and disease type). Results: Within a median follow-up of 5.2 y, 9 patients experienced disease progression after a median interval of 2.1 y, whereas the remainder had ongoing disease control (5 with a partial response and 4 with stable disease). Eight of the 9 patients with progressive disease died from MTC after a median of 3.5 y after TKI initiation. A pretherapeutic SUVmean of more than 4.0 predicted a significantly shorter PFS (1.9 y vs. 5.2 y, P = 0.04). Furthermore, sustained high 18F-FDG uptake at 3 mo with a SUVmean of more than 2.8 tended to portend an unfavorable prognosis, with a PFS of 1.9 y (vs. 3.5 y, P = 0.3). Prolonged carcinoembryonic antigen doubling times were significantly correlated with longer PFS (r = 0.7) and OS (r = 0.76, P < 0.01). None of the other clinical parameters had prognostic significance. Conclusion: Pretherapeutic 18F-FDG PET/CT provides prognostic information in patients with advanced MTC scheduled for treatment with the TKI vandetanib. A low tumor metabolism with an SUVmean of less than 4.0 before treatment predicts a longer PFS.
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