Norbert Galldiks1,2,3, Veronika Dunkl4, Garry Ceccon4, Caroline Tscherpel4,5, Gabriele Stoffels5, Ian Law6, Otto M Henriksen6, Aida Muhic7, Hans S Poulsen7, Jan Steger4, Elena K Bauer4, Philipp Lohmann5, Matthias Schmidt8, Nadim J Shah5,9, Gereon R Fink4,5, Karl-Josef Langen5,10. 1. Department of Neurology, University Hospital Cologne, Josef-Stelzmann St. 9, 50937, Cologne, Germany. n.galldiks@fz-juelich.de. 2. Institute of Neuroscience and Medicine (INM-3, -4), Forschungszentrum Juelich, Leo-Brandt-St. 5, 52425, Juelich, Germany. n.galldiks@fz-juelich.de. 3. Center of Integrated Oncology (CIO), Universities of Cologne and Bonn, Cologne, Germany. n.galldiks@fz-juelich.de. 4. Department of Neurology, University Hospital Cologne, Josef-Stelzmann St. 9, 50937, Cologne, Germany. 5. Institute of Neuroscience and Medicine (INM-3, -4), Forschungszentrum Juelich, Leo-Brandt-St. 5, 52425, Juelich, Germany. 6. Department of Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. 7. Department of Oncology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. 8. Dept. of Nuclear Medicine, University Hospital Cologne, Cologne, Germany. 9. Department of Neurology, University Hospital Aachen, Aachen, Germany. 10. Department of Nuclear Medicine, University Hospital Aachen, Aachen, Germany.
Abstract
BACKGROUND: The goal of this prospective study was to compare the value of both conventional MRI and O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET for response evaluation in glioblastoma patients treated with bevacizumab plus lomustine (BEV/LOM) at first progression. METHODS: After chemoradiation with concomitant and adjuvant temozolomide, 21 IDH wild-type glioblastoma patients at first progression (age range, 33-75 years; MGMT promoter unmethylated, 81%) were treated with BEV/LOM. Contrast-enhanced MRI and FET-PET scans were performed at baseline and after 8-10 weeks. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios. Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the post-progression overall survival (OS) ≤/>9 months as the reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning OS using uni- and multivariate survival estimates. RESULTS: Early treatment response as assessed by RANO criteria was not predictive for an OS>9 months (P = 0.203), whereas relative reductions of all FET-PET parameters significantly predicted an OS>9 months (P < 0.05). The absolute MTV at follow-up enabled the most significant OS prediction (sensitivity, 85%; specificity, 88%; P = 0.001). Patients with an absolute MTV below 5 ml at follow-up survived significantly longer (12 vs. 6 months, P < 0.001), whereas early responders defined by RANO criteria lived only insignificantly longer (9 vs. 6 months; P = 0.072). The absolute MTV at follow-up remained significant in the multivariate survival analysis (P = 0.006). CONCLUSIONS: FET-PET appears to be useful for identifying responders to BEV/LOM early after treatment initiation.
BACKGROUND: The goal of this prospective study was to compare the value of both conventional MRI and O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET for response evaluation in glioblastomapatients treated with bevacizumab plus lomustine (BEV/LOM) at first progression. METHODS: After chemoradiation with concomitant and adjuvant temozolomide, 21 IDH wild-type glioblastomapatients at first progression (age range, 33-75 years; MGMT promoter unmethylated, 81%) were treated with BEV/LOM. Contrast-enhanced MRI and FET-PET scans were performed at baseline and after 8-10 weeks. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios. Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the post-progression overall survival (OS) ≤/>9 months as the reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning OS using uni- and multivariate survival estimates. RESULTS: Early treatment response as assessed by RANO criteria was not predictive for an OS>9 months (P = 0.203), whereas relative reductions of all FET-PET parameters significantly predicted an OS>9 months (P < 0.05). The absolute MTV at follow-up enabled the most significant OS prediction (sensitivity, 85%; specificity, 88%; P = 0.001). Patients with an absolute MTV below 5 ml at follow-up survived significantly longer (12 vs. 6 months, P < 0.001), whereas early responders defined by RANO criteria lived only insignificantly longer (9 vs. 6 months; P = 0.072). The absolute MTV at follow-up remained significant in the multivariate survival analysis (P = 0.006). CONCLUSIONS:FET-PET appears to be useful for identifying responders to BEV/LOM early after treatment initiation.
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