Ulrich Roelcke1, Matthias T Wyss1, Martha Nowosielski1, Roberta Rudà1, Patrick Roth1, Silvia Hofer1, Norbert Galldiks1, Flavio Crippa1, Michael Weller1, Riccardo Soffietti1. 1. Department of Neurology and Brain Tumor Center, Cantonal Hospital, Aarau, Switzerland (U.R.); Institute for Pharmacology and Toxicology, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Neuroscience Center, ETH and University of Zürich, Zürich, Switzerland (M.T.W.); Department of Neurology, Medical University, Innsbruck, Austria (M.N.); Department of Neuro-Oncology, University Hospital, Torino, Italy (R.R., R.S.); Department of Neurology, University Hospital, Switzerland (P.R., M.W.); Department of Oncology, University Hospital, Zürich, Switzerland (S.H.); Department of Neurology, University Hospital, Cologne, Germany, and Research Center, Jülich, Germany (N.G.); Medicina Nucleare, Istituto Nazionale dei Tumori, Milano, Italy (F.C.).
Abstract
BACKGROUND: Patients with WHO grade II glioma may respond to chemotherapy that is currently not standardized regarding timing and treatment duration. Metabolic changes during chemotherapy may precede structural tumor volume reductions. We therefore compared time courses of amino acid PET and MRI responses to temozolomide (TMZ) and assessed whether responses correlated with seizure control and progression-free survival (PFS). METHODS: PET and MRI were performed before and during TMZ chemotherapy. Tumor volumes were calculated using regions-of-interest analysis. Amino acid uptake was also quantified as metabolically active tumor volume and tumor-to-cerebellum uptake ratio. RESULTS: One hundred twenty-five PET and 125 MRI scans from 33 patients were analyzed. Twenty-five patients showed metabolic responses that exhibited an exponential time course with a 25% reduction of the active volume on average after 2.3 months. MRI responses followed a linear course with a 25% reduction after 16.8 months. Reduction of metabolically active tumor volumes, but not reduction of PET uptake ratios or MRI tumor volumes, correlated with improved seizure control following chemotherapy (P = .012). Receiver-operating-characteristic curve analysis showed that a decrease of the active tumor volume of ≥80.5% predicts a PFS of ≥60 months (P = .018) and a decrease of ≥64.5% a PFS of ≥48 months (P = .037). CONCLUSIONS: Amino acid PET is superior to MRI for evaluating TMZ responses in WHO grade II glioma patients. The response delay between both imaging modalities favors amino acid PET for individually tailoring the duration of chemotherapy. Additional studies should investigate whether this personalized approach is appropriate with regard to outcome.
BACKGROUND:Patients with WHO grade II glioma may respond to chemotherapy that is currently not standardized regarding timing and treatment duration. Metabolic changes during chemotherapy may precede structural tumor volume reductions. We therefore compared time courses of amino acid PET and MRI responses to temozolomide (TMZ) and assessed whether responses correlated with seizure control and progression-free survival (PFS). METHODS: PET and MRI were performed before and during TMZ chemotherapy. Tumor volumes were calculated using regions-of-interest analysis. Amino acid uptake was also quantified as metabolically active tumor volume and tumor-to-cerebellum uptake ratio. RESULTS: One hundred twenty-five PET and 125 MRI scans from 33 patients were analyzed. Twenty-five patients showed metabolic responses that exhibited an exponential time course with a 25% reduction of the active volume on average after 2.3 months. MRI responses followed a linear course with a 25% reduction after 16.8 months. Reduction of metabolically active tumor volumes, but not reduction of PET uptake ratios or MRI tumor volumes, correlated with improved seizure control following chemotherapy (P = .012). Receiver-operating-characteristic curve analysis showed that a decrease of the active tumor volume of ≥80.5% predicts a PFS of ≥60 months (P = .018) and a decrease of ≥64.5% a PFS of ≥48 months (P = .037). CONCLUSIONS: Amino acid PET is superior to MRI for evaluating TMZ responses in WHO grade II gliomapatients. The response delay between both imaging modalities favors amino acid PET for individually tailoring the duration of chemotherapy. Additional studies should investigate whether this personalized approach is appropriate with regard to outcome.
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