Abstract
DIPG is among the most devastating brain tumors in children, necessitating the development of novel treatment strategies and advanced imaging markers such as perfusion to adequately monitor clinical trials. This study investigated tumor perfusion and 3D segmented tumor volume as predictive markers for outcome in children with newly diagnosed DIPG. Imaging data were assessed at baseline, during, and after RT, and every other month thereafter until tumor progression for 35 patients (ages 2-16 years) with newly diagnosed DIPG enrolled in the phase I clinical study, NCT00472017. Patients were treated with conformal RT and vandetanib, a vascular endothelial growth factor receptor 2 inhibitor. Tumor perfusion increased and tumor volume decreased during combined RT and vandetanib therapy. These changes slowly diminished in follow-up scans until tumor progression. However, increased tumor perfusion and decreased tumor volume during combined therapy were associated with longer PFS. Apart from a longer OS for patients who showed elevated tumor perfusion after RT, there was no association for tumor volume and other perfusion variables with OS. Our results suggest that tumor perfusion may be a useful predictive marker for the assessment of treatment response and tumor progression in children with DIPG treated with both RT and vandetanib. The assessment of tumor perfusion yields valuable information about tumor microvascular status and its response to therapy, which may help better understand the biology of DIPGs and monitor novel treatment strategies in future clinical trials.
Highlights
BACKGROUND AND PURPOSEDIPG is among the most devastating brain tumors in children, necessitating the development of novel treatment strategies and advanced imaging markers such as perfusion to adequately monitor clinical trials
Tumor perfusion increased and tumor volume decreased during combined RT and vandetanib therapy
Increased tumor perfusion and decreased tumor volume during combined therapy were associated with longer PFS
Summary
Imaging data were assessed at baseline, during, and after RT, and every other month thereafter until tumor progression for 35 patients (ages 2–16 years) with newly diagnosed DIPG enrolled in the phase I clinical study, NCT00472017. Phase I Clinical Study The imaging study was conducted between June 2007 and August 2010 at our institution.[3] A total of 35 patients (15 boys, 20 girls; median age, 6 years; age range, 2–16 years) with newly diagnosed DIPG were enrolled. Conformal RT was given in 1.8-Gy fractions 5 days a week for 6 weeks, for a total dose of 54 Gy to the planned target volume. The outcome of patients enrolled in the phase I study remained poor, with a 1-year OS of 37.5% Ϯ 10.5% and a 2-year OS of 21.4% Ϯ 11%. 2 patients remain alive, with 1 patient free of progression 58 months after diagnosis.[3]
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