Prognostic Value of TSPO PET Before Radiotherapy in Newly Diagnosed IDH-Wild-Type Glioblastoma

Abstract

The 18-kDa translocator protein (TSPO) is gaining recognition as a relevant target in glioblastoma imaging. However, data on the potential prognostic value of TSPO PET imaging in glioblastoma are lacking. Therefore, we investigated the association of TSPO PET imaging results with survival outcome in a homogeneous cohort of glioblastoma patients. Methods: Patients were included who had newly diagnosed, histologically confirmed isocitrate dehydrogenase (IDH)-wild-type glioblastoma with available TSPO PET before either normofractionated radiotherapy combined with temozolomide or hypofractionated radiotherapy. SUV_max on TSPO PET, TSPO binding affinity status, tumor volumes on MRI, and further clinical data, such as O ⁶-alkylguanine DNA methyltransferase (MGMT) and telomerase reverse transcriptase (TERT) gene promoter mutation status, were correlated with patient survival. Results: Forty-five patients (median age, 63.3 y) were included. Median SUV_max was 2.2 (range, 1.0-4.7). A TSPO PET signal was associated with survival: High uptake intensity (SUV_max > 2.2) was related to significantly shorter overall survival (OS; 8.3 vs. 17.8 mo, P = 0.037). Besides SUV_max, prognostic factors for OS were age (P = 0.046), MGMT promoter methylation status (P = 0.032), and T2-weighted MRI volume (P = 0.031). In the multivariate survival analysis, SUV_max in TSPO PET remained an independent prognostic factor for OS (P = 0.023), with a hazard ratio of 2.212 (95% CI, 1.115-4.386) for death in cases with a high TSPO PET signal (SUV_max > 2.2). Conclusion: A high TSPO PET signal before radiotherapy is associated with significantly shorter survival in patients with newly diagnosed IDH-wild-type glioblastoma. TSPO PET seems to add prognostic insights beyond established clinical parameters and might serve as an informative tool as clinicians make survival predictions for patients with glioblastoma.

Keywords: glioma; prognostication; survival.

Graphical abstract

FIGURE 1.

Kaplan–Meier curves of OS for entire patient group using median split of SUV_max (A), age (B), MGMT promoter methylation status (C), and median split of tumor volume on T2-weighted MRI (T2 vol.) (D). ⊕ = methylated; ⊖ = unmethylated.

FIGURE 2.

(A) 76-y-old male patient with left precentral IDH–wild-type glioblastoma (MGMT promoter-methylated, telomerase reverse transcriptase promoter C228T mutation; TSPO HAB) before hypofractionated radiotherapy and temozolomide chemotherapy. Tumoral TSPO radioligand uptake was high (SUV_max, 2.4), and survival was short (OS, 4.5 mo). (B) 71-y-old female patient with left postcentral–parietal IDH–wild-type glioblastoma (MGMT promoter-methylated, telomerase reverse transcriptase promoter C250T mutation; TSPO MAB) before hypofractionated radiotherapy and temozolomide chemotherapy. Tumoral TSPO radioligand uptake was low (SUV_max, 1.8), and survival was long (OS, 25.8 mo). CE-T1w = contrast-enhanced T1-weighted.