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 5 0.037). Besides SUV max , prognostic factors for OS were age (P 5 0.046), MGMT promoter methylation status (P 5 0.032), and T2-weighted MRI volume (P 5 0.031). In the multivariate survival analysis, SUV max in TSPO PET remained an independent prognostic factor for OS (P 5 0.023), with a hazard ratio of 2.212 (95% CI, 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.

Remote Neuroinflammation in Newly Diagnosed Glioblastoma Correlates with Unfavorable Clinical Outcome

“…3E ), also after adjustment for age, sex, the TSPO SNP and initiation of glucocorticoid medication prior to PET as covariates (F 1,25 = 7.01, p = 0.014). Testing previously evaluated parameters and indices (22) ( Supplemental Table 1 ), a significant impact on survival in the current cohort was identified by univariate Cox regression for age (HR: 1.06, p = 0.015), subsequent radiotherapy (HR: 0.27, p = 0.024) and chemotherapy (HR: 0.31, p = 0.003) as well as TSPO-PET signal of the tumor (HR: 1.85, p = 0.024), T1 contrast enhanced volumes (HR: 1.03, p < 0.001) and T2 hyperintensity volumes (HR: 1.02, p < 0.001). Furthermore, high contralateral TSPO-PET signal was associated with shorter survival in univariate Cox regression (HR: 1.72, p < 0.001; Log-rank test after median split: Χ² = 4.22, p = 0.040, Fig.…”

“…3F ). We proceeded with a multivariate Cox regression model including significant indices as well as MGMT, which likely did not reach significance in univariate Cox regression due to the lower sample size compared to a previous study (22), and glucocorticoid medication due to borderline significance. Here, high contralateral TSPO-PET signal was an independent predictor of shorter overall survival within the group of patients with glioblastoma (median OS: 6.5 vs 13.4 months, HR: 2.18, p = 0.005), together with age (HR: 1.12, p < 0.001), MGMT (HR: 0.20, p = 0.010), glucocorticoid medication (HR: 5.16, p = 0.011), and T1 contrast enhanced volume (HR: 1.04, p = 0.025; Supplemental Table 2 ).…”

“…Multivariate Cox regression was additionally controlled for initiation of glucocorticoid medication prior to TSPO-PET to exclude confounding effects of steroids on TSPO expression. Furthermore MGMT was included due to significant impact on survival in an extended cohort (22). As a validation, a multivariate Cox regression was performed including all tested variables.…”

Enhancing predictability of IDH mutation status in glioma patients at initial diagnosis: a comparative analysis of radiomics from MRI, [18F]FET PET, and TSPO PET

“…Our results highlight the value of static TSPO PET in predicting IDH mutation status, particularly in situations where dynamic [ 18 F]FET PET data have not been acquired. While TSPO PET is not intended to replace the well-understood and well-established [ 18 F]FET PET, its high performance has further been demonstrated in terms of survival prediction even among homogeneous molecular entities [ 25 , 26 ]. Consequently, it emerges as a vital supplementary non-invasive tool for optimizing early patient management at the point of initial diagnosis.…”

“…Aside from delineating active tumor, [ 18 F]FET PET has proven its utility in identifying intratumoral heterogeneity and differentiating tumor recurrence from pseudoprogression [20,21]. Despite being less tumor-specific, PET imaging using radioligands targeting the translocator protein (TSPO), which is upregulated not only in tumor cells but also in activated microglia or macrophages, has demonstrated correlations with histologic tumor grade, specific transcriptional glioma subtypes, and survival [22][23][24][25][26][27]. A recent study revealed that there is no correlation between PET information and relative contrast enhancement on T1-weighted MRI [28].…”