Amide proton transfer imaging might predict survival and IDH mutation status in high-grade glioma

Abstract

Objectives To assess the utility of amide proton transfer (APT) imaging as an imaging biomarker to predict prognosis and molecular marker status in high-grade glioma (HGG, WHO grade III/IV). Methods We included 71 patients with pathologically diagnosed HGG who underwent preoperative MRI with APT imaging. Overall survival (OS) and progression-free survival (PFS) according to APT signal, clinical factors, MGMT methylation status, and IDH mutation status were analyzed. Multivariate Cox regression models with and without APT signal data were constructed. Model performance was compared using the integrated AUC (iAUC). Associations between APT signals and molecular markers were assessed using the Mann-Whitney test. Results High APT signal was a significant predictor for poor OS (HR = 3.21, 95% CI = 1.62-6.34) and PFS (HR = 2.22, 95% CI = 1.33-3.72) on univariate analysis. On multivariate analysis, high APT signals were an independent predictor of poor OS and PFS when clinical factors alone (OS: HR = 2.89; PFS: HR = 2.13), or in combination with molecular markers (OS: HR = 2.85; PFS: HR = 2.00), were included as covariates. The incremental prognostic value of APT signals was significant for OS and PFS. IDH-wild type was significantly associated with high APT signals (p = 0.001) when compared to IDH-mutant; however, there was no difference based on MGMT methylation status (p = 0.208). Conclusion High APT signal was a significant predictor of poor prognosis in HGG. APT data showed significant incremental prognostic value over clinical prognostic factors and molecular markers and may also predict IDH mutation status. Key Points • Amide proton transfer (APT) imaging is a promising prognostic marker of high-grade glioma.• APT signals were significantly higher in IDH-wild type compared to IDH-mutant high-grade glioma.• APT imaging may be valuable for preoperative screening and treatment guidance.

Clinical Imaging for Diagnostic Challenges in the Management of Gliomas: A Review

“…Togao and Honda reported that in 36 patients with a histologically proven glioma, APT signal intensity was elevated in high‐grade gliomas and there was a positive correlation with Ki‐67 . A retrospective analysis of 27 patients showed increased APTw signal in IDH wild‐type tumors compared with IDH mutant tumors, as confirmed in a second cohort of patients with glioblastoma . Other independent groups have confirmed these results, reporting an association between increased APTw signal with high‐grade histology, worse clinical outcomes, and IDH mutant status, but no association with MGMT methylation status .…”

<p>Vessel Size Imaging is Associated with IDH Mutation and Patient Survival in Diffuse Lower-Grade Glioma</p>

“…The extent of tumor resection was classified as total, subtotal (<100% and ≥75% of gross total removal), or partial (<75% of gross tumor removal) resection according to the integrative analysis of intraoperative impressions in surgery and postoperative MRI findings. 4 Multiple lobes and multiple lesions were defined as involvement of two or more lobes connected by direct routes of spread and multiple sites not connected by obvious routes of spread. 14 Progression-free survival (PFS) was defined as the time from diagnosis to tumor progression based on the Response Assessment in Neuro-Oncology (RANO) criteria 15,16 or the date of the last follow-up examination if the patient did not show disease progression.…”

“…30,31 Several studies obtained the same results as our study. For instance, Bio Joo et al indicated that extent of resection was not related to PFS and OS in high-grade glioma; 4 another study showed that there was no difference in either PFS or OS among the various histologies in WHO grade II gliomas; 32 Villanueva-Meyer et al indicated that the 1p/19q co-deletion is associated with the prognosis of patients with grade II gliomas, but there were no IDH wild-type tumors with 1p/19q codeletion among their cases. 14 Different from those cases, our patients have IDH wild-type LGG with 1p/19q codeletion, and Hameed et al revealed that 1p/19q codeletion was not a significant predictor of OS in LGGs.…”

“…Notably, IDH mutation occurs in the majority of LGGs and has been considered a critical prognostic molecular marker for LGG. 4 Patients with IDH-mutant LGGs have better outcomes and appear to be more sensitive to chemoradiotherapy than those with IDH wild-type LGGs. 5,6 Therefore, identification of IDH genotype is beneficial for predicting the prognosis of LGG patients and for determining therapeutic strategies.…”

“…1 Diffuse lower-grade glioma (LGG) is an infiltrative brain tumor consisting of WHO grade II and III neoplasms, which presents a more indolent course compared to glioblastoma (GBM, grade IV), 2,3 and LGG is also divided into a series of molecular subtypes based on isocitrate dehydrogenase (IDH) and 1p/19q co-deletion status according to the 2016 WHO classification. [1][2][3] The prognosis of patients with glioma is related to several clinical factors, such as age, extent of tumor resection, and treatment modality, 4 and correlates with molecular markers, such as IDH mutation, O6methylguanine-DNA methyltransferase promotor methylation, and 1p/19q co-deletion. Notably, IDH mutation occurs in the majority of LGGs and has been considered a critical prognostic molecular marker for LGG.…”