18F-FET-PET as a biomarker for therapy response in non-contrast enhancing glioma following chemotherapy

J Neurooncol. 2018 Sep;139(3):721-730. doi: 10.1007/s11060-018-2919-0. Epub 2018 Jun 8.

Abstract

Background: Monitoring treatment response after chemotherapy of gadolinium-(Gd)-negative gliomas is challenging as conventional MRI often indicates no radiological changes. We hypothesize that 18F-FET-PET can be used as a biomarker for response assessment in Gd-negative gliomas undergoing chemotherapy.

Methods: Sixty-one patients harboring Gd-negative WHO grade II or III glioma receiving alkylating agents (temozolomide or CCNU/procarbacine) were included. All patients underwent MRI and 18F-FET-PET before chemotherapy and 6 months later. We calculated T2-volume, 18F-FET-PET based biological tumour volume (BTV) and maximal tumour-to-brain ratio (TBRmax). Moreover, dynamic PET acquisition was performed using time-activity-curves (TACs) analysis. For MRI-based response assessment, RANO criteria for low-grade glioma were used. For 18F-FET-PET, following classification scheme was tested: responsive disease (RD) when a decrease in either BTV ≥ 25% and/or TBRmax ≥ 10% occurred, an increase in BTV ≥ 25% and/or TBRmax increase > 10% characterized progressive disease (PD), minor changes ± 25% for BTV and ± 10% for TBRmax were regarded as stable disease (SD). Post-chemotherapy survival (PCS) and time-to-treatment failure (TTF) were calculated using the Kaplan-Meier method.

Results: 18F-FET-PET based response has shown patients with RD to have the longest TTF time (78.5 vs 24.6 vs 24.1 months, p = 0.001), while there was no significant difference between patients with a SD and PD. A comparable pattern was observed for PCS (p < 0.001). T2-volume based assessment was not associated with outcome.

Conclusion: 18F-FET-PET is a promising biomarker for early response assessment in Gd-negative gliomas undergoing chemotherapy. It might be helpful for a timely adjustment of potentially ineffective treatment concepts and overcomes limitations of conventional structural imaging.

Keywords: Chemotherapy; FET-PET; Glioma; Metabolic response.

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / metabolism
  • Brain Neoplasms / diagnostic imaging*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Contrast Media
  • Female
  • Follow-Up Studies
  • Gadolinium
  • Glioma / diagnostic imaging*
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Positron-Emission Tomography*
  • Radiopharmaceuticals
  • Tyrosine / analogs & derivatives

Substances

  • Antineoplastic Agents
  • Contrast Media
  • Radiopharmaceuticals
  • (18F)fluoroethyltyrosine
  • Tyrosine
  • Gadolinium