Molecular Alterations and Their Correlation With the Survival of Glioblastoma Patients With Corpus Callosum Involvement.

Meng Cui,Yihong Chi,Xin Gao,Meng Zhang,Hepu Lin,Hewen Chen,Caihong Sun,Xiaodong Ma

doi:10.3389/fnins.2021.701426

Abstract

Purpose: To explore molecular alterations and their correlation with the survival of patients with glioblastoma (GBM) with corpus callosum (CC) involvement (ccGBM).Methods: Electronic medical records were reviewed for glioma patients tested for molecular alterations and treated at our hospital between January 2016 and July 2020. ccGBM was compared to GBM without CC involvement (non-ccGBM) to identify differences in molecular alterations. Clinical outcomes and survival were compared between ccGBM and non-ccGBM patients, as well as among patients with ccGBM with different molecular alteration statuses. ccGBM was also compared to diffuse midline glioma (DMG) to clarify their correlation in molecular alterations, the progression-free survival (PFS), and overall survival (OS).Results: Thirty ccGBM and 88 non-ccGBM patients were included. PDGFRA amplification (PDGFRAamp, 33.3 vs. 9.1%, P = 0.004) and missense mutation (PDGFRAmut, 20.0 vs. 3.4%, P = 0.011) both had higher incidences in ccGBM than in non-ccGBM. PDGFRA alteration was associated with the occurrence of ccGBM (OR = 4.91 [95% CI: 1.55–15.52], P = 0.007). ccGBM with PDGFRAamp resulted in a shorter median PFS (8.6 vs. 13.5 months, P = 0.025) and OS (12.4 vs. 17.9 months, P = 0.022) than non-ccGBM with PDGFRAnon-amp. ccGBM with PDGFRAamp combined with PDGFRAmut (PDGFRAamp-mut) had a shorter median PFS (7.6 vs. 8.9 months, P = 0.022) and OS (9.6 vs. 17.8 months, P = 0.006) than non-ccGBM with wild-type PDGFRA and no amplification (PDGFRA-w, non-amp). Compared to ccGBM with PDGFRA-w, non-amp, ccGBM with PDGFRAamp and PDGFRAamp-mut both had a shorter median PFS and OS (P < 0.05). The hazard ratios (HRs) of PDGFRAamp for PFS and OS in ccGBM were 3.08 (95% CI: 1.02–9.35, P = 0.047) and 5.07 (1.52–16.89, P = 0.008), respectively, and the HRs of PDGFRAamp-mut for PFS and OS were 13.16 (95% CI: 3.19–54.40, P < 0.001) and 16.36 (2.66–100.70, P = 0.003). ccGBM may have similar incidences of PDGFRAamp or mut (PDGFRAamp/mut) as DMG, and they also had similar median PFS (10.9 vs. 9.0 months, P = 0.558) and OS (16.8 vs. 11.5 months, P = 0.510).Conclusion:PDGFRA alterations are significantly associated with the occurrence and poor prognosis of ccGBM. ccGBM with PDGFRAamp/mut may be classified as a single subtype of GBM that has a similar survival rate to DMG. PDGFR inhibitors may be a promising treatment method for ccGBM.

Highlights

MATERIALS AND METHODSGlioblastoma (GBM) is highly malignant tumor (World Health Organization [WHO] grade IV), with an annual incidence of 3.1 per 100,000 and a 5-year survival rate of less than 3% (Ohgaki, 2009; Wirsching et al, 2016)
The ccGBM group had a higher incidence of platelet derived growth factor receptor alpha (PDGFRA) amplification (PDGFRAamp) (33.3 vs. 9.1%, P = 0.004) and PDGFRA mutation (PDGFRAmut) (20.0 vs. 3.4%) than the non-ccGBM group
Other molecular alterations that were significantly associated with the prognosis of glioma are shown in Table 1, but none of them were identified to be different between the ccGlioma group and non-ccGlioma group (Figure 1)

Summary

Introduction

MATERIALS AND METHODSGlioblastoma (GBM) is highly malignant tumor (World Health Organization [WHO] grade IV), with an annual incidence of 3.1 per 100,000 and a 5-year survival rate of less than 3% (Ohgaki, 2009; Wirsching et al, 2016). As the largest interhemispheric fiber bundle in the human brain, the corpus callosum (CC) is frequently invaded by GBM (Nazem-Zadeh et al, 2012). GBM with CC involvement (ccGBM) can be classified into two types. The other type is known as butterfly GBM (bGBM) and involves the corpus callosum and both cerebral hemispheres (Louis et al, 2007; Nazem-Zadeh et al, 2012; Ho et al, 2013; Komori, 2017). CcGBM has a poorer prognosis than GBM without CC involvement (non-ccGBM) and is associated with incomplete resection or residual tumor after surgery (Talos et al, 2006). The present consensus is that ccGBM has a poorer prognosis than common GBM regardless of whether resection is performed (Chen et al, 2015; Liang et al, 2016)

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