Multimodal imaging-defined subregions in newly diagnosed glioblastoma: impact on overall survival

Neuro Oncol. 2019 Feb 14;21(2):264-273. doi: 10.1093/neuonc/noy169.

Abstract

Background: Although glioblastomas are heterogeneous brain-infiltrating tumors, their treatment is mostly focused on the contrast-enhancing tumor mass. In this study, we combined conventional MRI, diffusion-weighted imaging (DWI), and amino acid PET to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value.

Methods: Contrast-enhanced T1, T2/fluid attenuated inversion recovery (FLAIR) MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[11C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients with newly diagnosed glioblastoma. Five tumor subregions were identified based on a combination of MRI contrast enhancement, T2/FLAIR signal abnormalities, and AMT uptake on PET. ADC and AMT uptake tumor/contralateral normal cortex (T/N) ratios in these tumor subregions were correlated, and their prognostic value was determined.

Results: A total of 115 MRI/PET-defined subregions were analyzed. Most tumors showed not only a high-AMT uptake (T/N ratio > 1.65, N = 27) but also a low-uptake subregion (N = 21) within the contrast-enhancing tumor mass. High AMT uptake extending beyond contrast enhancement was also common (N = 25) and was associated with low ADC (r = -0.40, P = 0.05). Higher AMT uptake in the contrast-enhancing tumor subregions was strongly prognostic for overall survival (hazard ratio: 7.83; 95% CI: 1.98-31.02, P = 0.003), independent of clinical and molecular genetic prognostic variables. Nonresected high-AMT uptake subregions predicted the sites of tumor progression on posttreatment PET performed in 10 patients.

Conclusions: Glioblastomas show heterogeneous amino acid uptake with high-uptake regions often extending into non-enhancing brain with high cellularity; nonresection of these predict the site of posttreatment progression. High tryptophan uptake values in MRI contrast-enhancing tumor subregions are a strong, independent imaging marker for longer overall survival.

Keywords: amino acid; diffusion-weighted imaging; glioblastoma; positron emission tomography; survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diffusion Magnetic Resonance Imaging / methods*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / metabolism
  • Glioblastoma / mortality*
  • Glioblastoma / pathology*
  • Humans
  • Male
  • Middle Aged
  • Multimodal Imaging / methods*
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology*
  • Positron-Emission Tomography / methods*
  • Prognosis
  • Survival Rate
  • Tryptophan / metabolism

Substances

  • Tryptophan