Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas

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.

Keywords: MRI; PET; chemotherapy; epilepsy; low-grade glioma.

Fig. 1.

Time course of imaging responses. (A) Examples of individual responses as measured with PET (filled symbols) and MRI (open symbols). Square: oligoastrocytoma (#12); triangle: oligodendroglioma (#16); diamond: astrocytoma (#6). (B and C) Data points represent pooled volume changes measured for the whole cohort of metabolic responders during chemotherapy before progression (ie, participants were censored at the last PET or MRI prior to progression. Black lines correspond to exponential fit for PET data (B) (y = 74.61 * exp(−x/158.86) + 24.31) and linear fit for MRI data (C) (y = 99.27–0.05 * x), respectively. Values on the y-axis represent percent volume changes compared with baseline (ie, before the start of chemotherapy).

Fig. 2.

Seizure control and imaging responses. Best imaging responses on active PET volume (A), mean T-to-CBL uptake ratio (B), MRI T₂ lesion size (C) in patients under stable antiepileptic drug doses (n = 17). Seizure control group I = reduction of seizure frequency by 0%–50%, seizure control group II = reduction >50% or seizure-free patients during chemotherapy. Figure 2A: *P = .012 (Mann-Whitney U test).