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Volumetric Analysis of ¹⁸F-FDG PET in Glioblastoma Multiforme: Prognostic Information and Possible Role in Definition of Target Volumes in Radiation Dose Escalation

¹ Department of Radiation Oncology, University of Washington Medical Center, Seattle, Washington
² Department of Nuclear Medicine, University of Washington Medical Center, Seattle, Washington
³ Department of Neurosurgery, University of Washington Medical Center, Seattle, Washington
⁴ Department of Neuro-Oncology, University of Washington Medical Center, Seattle, Washington

The use of ¹⁸F-FDG PET for brain tumors has been shown to be accurate in identifying areas of active disease. Radiation dose escalation in the treatment of glioblastoma multiforme (GBM) may lead to improved disease control. On the basis of these premises, we initiated a pilot study to investigate the use of ¹⁸F-FDG PET for the guidance of radiation dose escalation in the treatment of GBM. Methods: Patients were considered eligible to participate in the study if they had a diagnosis of GBM, were at least 18 y old, and had a score of at least 60 on the Karnofsky Scale. Patients were treated with standard conformal fractionated radiotherapy (1.8 Gy per fraction, to 59.4 Gy), with volumes defined by MRI. At a dose of 45–50.4 Gy, patients underwent ¹⁸F-FDG PET for boost target delineation. Final noncoplanar fields (3–4) were designed to treat the volume of abnormal ¹⁸F-FDG uptake plus a 0.5-cm margin for an additional 20 Gy (2 Gy per fraction), to a total dose of 79.4 Gy. If no abnormal ¹⁸F-FDG uptake was observed, treatment was stopped after the conventional course of 59.4 Gy. Age, Karnofsky score, MRI-based volumes, and ¹⁸F-FDG PET volume were analyzed as prognostic variables for time to tumor progression (TTP) and overall survival. ¹⁸F-FDG PET volumes and MRI-based volumes were compared to assess concordance. Results: For the 27 patients who could be evaluated, median actuarial TTP was 43 wk, and median actuarial survival was 70 wk. On univariate analysis, ¹⁸F-FDG PET, T1-weighted MRI gadolinium enhancement (excluding nonenhancing resection cavity), and T2-weighted MRI volumes were significantly predictive of TTP. On multivariate analysis, only ¹⁸F-FDG PET volume retained significance for predicting TTP. Similar results were obtained on analysis of these variables as prognostic factors for survival. When ¹⁸F-FDG PET-based volumes were compared with MRI-based volumes, a difference of at least 25% was detected in all patients, with all but 2 having smaller ¹⁸F-FDG PET volumes. Of patients in whom ¹⁸F-FDG uptake was initially present but treatment subsequently failed, 83% demonstrated the first tumor progression within the region of abnormal ¹⁸F-FDG uptake. Conclusion: In comparison with MRI, ¹⁸F-FDG PET defined unique volumes for radiation dose escalation in the treatment of GBM. ¹⁸F-FDG PET volumes were predictive of survival and time to tumor progression in the treatment of patients with GBM.

Key Words: glioblastoma multiforme • PET • radiation dose escalation

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