This is a retrospective observational study approved by the Institutional Review Board and Ethics Committee (Project No 900717). 171 patients of World Health Organisation (WHO) Grade III and IV glioma, were studied. Patients first visited the Neuro-oncology out-patient department (OPD) following which, they underwent treatment as per institutional protocol for WHO Grade 3 and Grade 4 glial tumors. Patients subsequently were discussed in a joint neuro-oncology meeting (JNOM), which is an institutional multi-disciplinary clinic. FET PET was advised thereafter to differentiate between post treatment changes and recurrence. Patients referred for FET PET between 1st April 2017 and 30th April 2022, with a follow-up period of 18 months, were included in the study. Patient characteristics have been given in Table 1.

Patients who were referred for FET PET after a multidisciplinary Joint Clinic decision were included in the study. These patients had a histopathological diagnosis of higher grade glioma (WHO Grade III or IV), and either underwent surgery followed by radiotherapy, or were deemed inoperable and received upfront radiotherapy. All patients received concurrent Temozolomide (TMZ) for 6 months, followed by adjuvant TMZ for 12 months, as the standard institutional protocol. All patients included in this study had a disease free period of at least 3 months following treatment completion and reported to OPD with clinical symptoms or equivocal MR findings. FET PET imaging was performed not later than 15 days from MRI. Following were the equivocal MRI findings which led to referral of patients for FET PET: (1) progressive or new contrast-enhancing lesion(s) on post contrast T1 or non-enhancing lesion(s) on T2/fluid-attenuated inversion recovery (FLAIR) MRI sequences, where the distinction between disease recurrence and posttreatment changes was uncertain, (2) irregular enhancement (‘Swiss Cheese’ pattern) typical for post-treatment changes in patients which showed areas of hyperperfusion and/or abnormal spectroscopy findings on MR imaging (3) patient showing clinical worsening with MR showing typical appearance of post-treatment changes. The above-mentioned referral pattern had 86, 48 and 37 patients in each subset, respectively.

Liesche et al. showed that dynamic PET parameters relied on tumor vascularity which was dependent on the extent of neovasuclarisation; and it was better depicted by MR perfusion imaging [10]. Static imaging at 20 min purely assesses the amino-acid receptor expression. In addition, a single-point imaging was justified in terms of scan time, costs, and patient turnover in a busy department. Patients were injected with 185–222 MBq of Fluorinated (Fluorine-18 labeled) Fluoro-ethyl tyrosine (FET). Dedicated static imaging of the brain was performed at 20 min post injection using Philips Gemini TF TOF 16/64 PET/CT scanners (PET crystal-LYSO). After obtaining a scout image, a plain and post contrast CT scan of the brain was performed in craniocaudal direction (120 kV, 250 mAs/slice, thickness-3 mm, increment − 1.5 mm, pitch of 0.9 and FOV of 300 mm). PET scanning was performed immediately after the CT acquisition in 3D mode, without changing the patient position. Single bed position was acquired, for duration of 5 min. Images were reconstructed iteratively using the row action maximum likelihood algorithm (RAMLA) algorithm. CT attenuation correction, dead time correction, and decay correction were applied.

Reconstructed fused PET/CT images were viewed on Extended brilliance workspace (EBW) version 4.5, Philips Healthcare. Two independent Nuclear Medicine physicians, who were blinded to the MR findings, multi-disciplinary clinic discussions and histopathology; processed and reported the studies. Tumor to background ratio (TBR) was used as a semi quantitative parameter for image interpretation. It is defined as ratio of SUVmax of the lesion to the SUV mean of contralateral white matter. Background region-of-interest was based on recommendations in EANM, SNMMI, EANO, and RANO guidelines. A crescent-shaped volume of interest (VOI) was drawn in relation to healthy-appearing brain tissue in the hemisphere contralateral to the tumour including grey and white matter in the frontal lobe in six adjacent slices. A cut-off of 2.5 for tumor to white matter ratio was used to differentiate between tumor recurrence (TR) and treatment related changes (TRC). Positive FET study was suggestive of TR with a TBR of greater than 2.5, whereas negative FET study depicted TRC with TBR less than or equal to 2.5. Subsequently, the imaging findings were confirmed with either histopathological diagnosis in a multidisciplinary joint clinic or based on radiological or clinical follow up of patients.

The standard protocol for follow-up at our institution involves MR imaging and clinic visit at 6 and 12 months post-treatment completion, and annually thereafter. If the patient is symptomatic, the patient visits the clinic and MR is performed and discussed in a multidisciplinary clinic. In our study, following FET PET, patients underwent clinical follow-up and MR imaging every 3 months for the first 6 months and every 6 months thereafter. In all, 16 patients underwent surgery and histopathological confirmation was available.

The diagnostic performance of the TBR for differentiation between TR and TRC was assessed by receiver-operating-characteristic curve analyses using the neuropathologic results or the clinicoradiological follow-up as a reference.