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

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

JOURNAL=Frontiers in Neuroscience

VOLUME=15

YEAR=2021

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2021.701426

DOI=10.3389/fnins.2021.701426

ISSN=1662-453X

ABSTRACT=<p><bold>Purpose:</bold> To explore molecular alterations and their correlation with the survival of patients with glioblastoma (GBM) with corpus callosum (CC) involvement (ccGBM).</p><p><bold>Methods:</bold> 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).</p><p><bold>Results:</bold> Thirty ccGBM and 88 non-ccGBM patients were included. <italic>PDGFRA</italic> amplification (<italic>PDGFRAamp</italic>, 33.3 vs. 9.1%, <italic>P</italic> = 0.004) and missense mutation (<italic>PDGFRAmut</italic>, 20.0 vs. 3.4%, <italic>P</italic> = 0.011) both had higher incidences in ccGBM than in non-ccGBM. <italic>PDGFRA</italic> alteration was associated with the occurrence of ccGBM (OR = 4.91 [95% CI: 1.55–15.52], <italic>P</italic> = 0.007). ccGBM with <italic>PDGFRAamp</italic> resulted in a shorter median PFS (8.6 vs. 13.5 months, <italic>P</italic> = 0.025) and OS (12.4 vs. 17.9 months, <italic>P</italic> = 0.022) than non-ccGBM with <italic>PDGFRAnon-amp</italic>. ccGBM with <italic>PDGFRAamp</italic> combined with <italic>PDGFRAmut</italic> (<italic>PDGFRAamp-mut</italic>) had a shorter median PFS (7.6 vs. 8.9 months, <italic>P</italic> = 0.022) and OS (9.6 vs. 17.8 months, <italic>P</italic> = 0.006) than non-ccGBM with wild-type <italic>PDGFRA</italic> and no amplification (<italic>PDGFRA-w, non-amp</italic>). Compared to ccGBM with <italic>PDGFRA-w, non-amp</italic>, ccGBM with <italic>PDGFRAamp</italic> and <italic>PDGFRAamp-mut</italic> both had a shorter median PFS and OS (<italic>P</italic> &lt; 0.05). The hazard ratios (HRs) of <italic>PDGFRAamp</italic> for PFS and OS in ccGBM were 3.08 (95% CI: 1.02–9.35, <italic>P</italic> = 0.047) and 5.07 (1.52–16.89, <italic>P</italic> = 0.008), respectively, and the HRs of <italic>PDGFRAamp-mut</italic> for PFS and OS were 13.16 (95% CI: 3.19–54.40, <italic>P</italic> &lt; 0.001) and 16.36 (2.66–100.70, <italic>P</italic> = 0.003). ccGBM may have similar incidences of <italic>PDGFRAamp</italic> or <italic>mut</italic> (<italic>PDGFRAamp/mut</italic>) as DMG, and they also had similar median PFS (10.9 vs. 9.0 months, <italic>P</italic> = 0.558) and OS (16.8 vs. 11.5 months, <italic>P</italic> = 0.510).</p><p><bold>Conclusion:</bold><italic>PDGFRA</italic> alterations are significantly associated with the occurrence and poor prognosis of ccGBM. ccGBM with <italic>PDGFRAamp/mut</italic> 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.</p>