Dynamic 18F-FET PET is a powerful imaging biomarker in gadolinium-negative gliomas

Neuro Oncol. 2019 Feb 14;21(2):274-284. doi: 10.1093/neuonc/noy098.

Abstract

Background: We aimed to elucidate the place of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in prognostic models of gadolinium (Gd)-negative gliomas.

Methods: In 98 patients with Gd-negative gliomas undergoing 18F-FET PET guided biopsy, time activity curves (TACs) of each tumor were qualitatively categorized as either increasing or decreasing. Additionally, post-hoc quantitative analyses were done using minimal time-to-peak (TTPmin) measurements. Prognostic factors were obtained from multivariate hazards models. The fit of the biospecimen- and imaging-derived models was compared.

Results: A homogeneous increasing, mixed, and homogeneous decreasing TAC pattern was seen in 51, 19, and 28 tumors, respectively. Mixed TAC tumors exhibited both increasing and decreasing TACs. Corresponding adjusted 5-year survival was 85%, 47%, and 19%, respectively (P < 0.001). Qualitative and quantitative TAC measurements were highly intercorrelated (P < 0.0001). TTPmin was longest (shortest) in the homogeneous increasing (decreasing) TAC group and in between in the mixed TAC group. TTPmin was longer in isocitrate dehydrogenase (IDH)-mutant tumors (P < 0.001). Outcome was similarly precisely predicted by biospecimen- and imaging-derived models. In the biospecimen model, World Health Organization (WHO) grade (P < 0.0001) and IDH status (P < 0.001) were predictors for survival. Outcome of homogeneous increasing (homogeneous decreasing) TAC tumors was nearly identical, with both TTPmin > 25 min (TTPmin ≤ 12.5 min) tumors and IDH-mutant grade II (IDH-wildtype) gliomas. Outcome of mixed TAC tumors matched that of both intermediate TTPmin (>12.5 min and ≤25 min) and IDH-mutant, grade III gliomas. Each of the 3 prognostic clusters differed significantly from the other ones of the respective models (P < 0.001).

Conclusion: TAC measurements constitute a powerful biomarker independent from tumor grade and IDH status.

Keywords: 18F-FET PET; biomarkers; glioma; prognosis; targeted therapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Female
  • Follow-Up Studies
  • Gadolinium / metabolism*
  • Glioma / diagnostic imaging
  • Glioma / metabolism
  • Glioma / pathology*
  • Glioma / surgery
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Recurrence, Local / surgery
  • Positron-Emission Tomography / methods*
  • Prognosis
  • Prospective Studies
  • Survival Rate
  • Tyrosine / analogs & derivatives*
  • Tyrosine / metabolism

Substances

  • Biomarkers, Tumor
  • (18F)fluoroethyltyrosine
  • Tyrosine
  • Gadolinium