Vascular biomarkers derived from dynamic contrast-enhanced MRI predict response of vestibular schwannoma to antiangiogenic therapy in type 2 neurofibromatosis.

Ka-Loh Li, Ibrahim Djoukhadar, Xiaoping Zhu, Sha Zhao, Simon Lloyd, Martin Mccabe, Catherine McBain, Gareth Evans, Alan Jackson

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Abstract

BACKGROUND: Antiangiogenic therapy of vestibular schwannoma (VS) in type 2 neurofibromatosis can produce tumor shrinkage with response rates of 40%-60%. This study examines the predictive value of parameter-derived MRI in this setting. METHODS: Twelve patients with 20 VSs were recruited. Each had at least one rapidly growing tumor. Patients were treated with bevacizumab, 5 mg/kg every 2 weeks. Patients with stable or reduced VS volume were maintained at 2.5-5 mg every 4 weeks after 6 months. Those who failed treatment had their bevacizumab discontinued. Dynamic contrast-enhanced (DCE) MRI performed prior to treatment using a high temporal resolution technique, and data were analyzed to allow measurement of contrast transfer coefficient (K(trans)), vascular fraction (vp), extravascular-extracellular fraction (ve). Relaxation rate (R1N) was measured using a variable flip angle technique. Apparent diffusional coefficient (ADC) was calculated from diffusion-weighted imaging. The predictive power of microvascular parameters and ADC were examined using logistic regression modeling. RESULTS: Responding tumors were larger (P <.001), had lower R1N (P <.001), and higher K(trans) (P <.05) and ADC (P <.01). They showed increases in R1N (P <.01) and reduction of K(trans) (P <.01) and ADC (P <.01). Modeling to predict response demonstrated significant independent predictive power for R1N (Î’ = - 0.327, P <.001), and K(trans) (Î’ = 0.156, P <.05). Modeling to predict percentage change in tumor volume at 90 days identified baseline tumor volume (Î’ = 5.503, P <.05), R1N (Î’ = - 5.844, P <.05), and K(trans) (Î’ = 5.622, P <.05) as independent significant predictors. CONCLUSIONS: In patients with type 2 neurofibromatosis, biomarkers from DCE-MRI are predictive of VS volume response to inhibition of vascular endothelial growth factor inhibition.
Original languageEnglish
Article number26311690
Pages (from-to)275-282
Number of pages7
JournalNeuro-Oncology
Volume18
Issue number2
DOIs
Publication statusPublished - 26 Aug 2015

Keywords

  • bevacizumab, DCE-MRI, neurofibromatosis type 2, prediction treatment response

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