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Abstract
Objective: The aim of this prospective longitudinal study was to identify static and dynamic O-(2-[18F]fluoroethyl)-l-tyrosine PET (18FET-PET)-derived imaging biomarkers in patients with glioblastoma (GBM).
Methods: Seventy-nine patients with newly diagnosed GBM were included; 42 patients underwent stereotactic biopsy (unresectable tumors) and 37 patients microsurgical tumor resection. All patients were scheduled to receive radiotherapy plus concomitant and adjuvant temozolomide (RCx/TMZ). 18FET-PET evaluation using static and dynamic analysis was done before biopsy/resection, after resection, 4 to 6 weeks following RCx, and after 3 cycles of TMZ. Endpoints were survival and progression-free-survival. Prognostic factors were obtained from proportional hazards models.
Results: Biological tumor volume before RCx (BTVpreRCx) was the most important 18FET-PET–derived imaging biomarker and was independent of MGMT promoter methylation and clinical prognostic factors: patients with smaller BTVpreRCx had significantly longer progression-free and overall survival (OS). 18FET time-activity curves (TACs) before treatment and their changes after RCx were also related to outcome; patients with initially increasing TACs experienced longer OS.
Conclusion: BTVpreRCx and TAC represent important 18FET-PET–derived imaging biomarkers in GBM. Increasing TACs are associated with prolonged OS. The BTVpreRCx is a strong prognostic factor for progression-free survival and OS independent of the mode of surgery. Our data furthermore suggest that patients harboring resectable GBM might benefit from maximal PET-guided tumor resection.
GLOSSARY
- BG=
- background;
- BTV=
- biological tumor volume;
- EORTC/NCIC=
- European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada;
- 18FET-PET=
- O-(2-[18F]fluoroethyl)-l-tyrosine PET;
- FLAIR=
- fluid-attenuated inversion recovery;
- GBM=
- glioblastoma;
- Gd+=
- gadolinium enhanced;
- HR=
- hazard ratio;
- KPS=
- Karnofsky performance score;
- LBR=
- lesion to brain ratio;
- MGMT=
- O-6-methylguanine-DNA methyltransferase;
- OS=
- overall survival;
- PFS=
- progression-free survival;
- RCx=
- radiochemotherapy;
- ROC=
- receiver operating characteristic;
- SUV=
- standardized uptake value;
- TAC=
- time-activity curve;
- TMZ=
- temozolomide
Footnotes
↵* These authors contributed equally to this work.
↵† Deceased.
German Glioma Network coinvestigators are listed on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received June 5, 2014.
- Accepted in final form October 27, 2014.
- © 2015 American Academy of Neurology
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