Contribution of PET imaging to radiotherapy planning and monitoring in glioma patients - a report of the PET/RANO group

Abstract

The management of patients with glioma usually requires multimodality treatment including surgery, radiotherapy, and systemic therapy. Accurate neuroimaging plays a central role for radiotherapy planning and follow-up after radiotherapy completion. In order to maximize the radiation dose to the tumor and to minimize toxic effects on the surrounding brain parenchyma, reliable identification of tumor extent and target volume delineation is crucial. The use of positron emission tomography (PET) for radiotherapy planning and monitoring in gliomas has gained considerable interest over the last several years, but Class I data are not yet available. Furthermore, PET has been used after radiotherapy for response assessment and to distinguish tumor progression from pseudoprogression or radiation necrosis. Here, the Response Assessment in Neuro-Oncology (RANO) working group provides a summary of the literature and recommendations for the use of PET imaging for radiotherapy of patients with glioma based on published studies, constituting levels 1-3 evidence according to the Oxford Centre for Evidence-based Medicine.

Keywords: FDG; amino acid PET; glioblastoma; radiation injury; target volume.

Fig. 1

Patient with a multifocal IDH-wild-type glioblastoma. The extent of increased FET uptake based on a tumor-to-background threshold of >1.6 (left image; red contour transferred onto MR images) is considerably larger than the contrast enhancement (middle image) and the extent of the signal hyperintensity on the T2-weighted MR image (right image). Abbreviations: FET, O-(2-[¹⁸F]-fluoroethyl)-l-tyrosine; IDH, isocitrate dehydrogenase.

Fig. 2

Patient with a progressive IDH-wild-type glioblastoma 12 months after first-line chemoradiation with temozolomide (2.0/1.8 Gy × 30 using the radiation technique volumetric modulated arc therapy (VMAT); 60 Gy to the metabolically active occipital lesion, and 54 Gy to the non-enhancing T2 hyperintense parahippocampal lesion). After neuropathological confirmation of multifocal progression using stereotactic biopsy, FET PET was used to define the re-irradiation target volume (3.0 Gy × 13; FET PET-based PTV in red). Importantly, the re-irradiation target volume based on conventional MRI (MRI-based PTV in yellow) is considerably smaller. VMAT plan (bottom right) with 37.05 Gy (green), 31.2 Gy (light blue), 20 Gy (blue), and 15 Gy (dark blue) isodose lines. Abbreviations: FET, O-(2-[¹⁸F]-fluoroethyl)-l-tyrosine; IDH, isocitrate dehydrogenase; PET, positron emission tomography.

Fig. 3

FET PET and conventional MR images of a 67-year-old patient with an IDH-wild-type glioblastoma with methylated MGMT promoter before radiotherapy plus of lomustine-temozolomide chemotherapy (left column). Nine weeks after radiotherapy, conventional MRI 9 suggests tumor progression (right column). In contrast, follow-up FET PET shows a substantial decrease of metabolic activity compared to the baseline scan and is consistent with pseudoprogression. The maximum tumor/brain ratios (TBR) decreased from 5.1 to 3.0 (41%). Abbreviations: FET, O-(2-[¹⁸F]-fluoroethyl)-l-tyrosine; IDH, isocitrate dehydrogenase; PET, positron emission tomography.