Peri-tumoral brain edema associated with glioblastoma correlates with tumor recurrence

Abstract

Glioblastoma is the most common malignant tumor of the brain. Despite advances in treatment, the prognosis for the condition has remained poor. Glioblastoma is often associated with peritumoral brain edema (PTBE), which can result in increased intracranial pressure and devastating neurological sequelae if left untreated. Surgery is the main treatment for glioblastoma, however current international surgical guidelines do not specify whether glioblastoma-induced PTBE tissue should be resected. In this study, we analyzed treatment outcomes of PTBE using surgical resection. We performed a retrospective analysis of 255 cases of glioblastoma between 2014 and 2016, and found that a significant proportion of patients had a degree of PTBE. We found that surgical resection led to reduction in midline shift that had resulted from edema, however, postoperative complications and KPS scores were not significantly different in the two conditions. We also observed a delay in glioblastoma recurrence in patients undergoing PTBE tissue resection vs patients without resection of PTBE tissue. Interestingly, there was an abnormal expression of tumor associated genes in PTBE, which has not been previously been found. Taken together, this study indicates that glioblastoma-induced PTBE should be investigated further particularly as the tumor microenvironment is a known therapeutic target and therefore interactions between the microenvironment and PTBE should be explored. This study also highlights the importance of resection of PTBE tissue to not only reduce the mechanical obstruction associated with edema but also to delay recurrence of glioblastoma.

Keywords: Glioblastoma; Peritumoral brain edema; Recurrence; Tumor resection..

Figure 1

Warburg effect and tumor growth

Figure 2

Glioblastoma induces peritumoral brain edema. All the tumors are located in the cortex: Frontal lobe, Occipital lobe, Parietal lobe, Temporal lobe. Before the operative, these patients are accompanied by peritumoral brain edema.

Figure 3

Surgical resection of PTBE is clinically based on the condition of patients. All the patients are accompanied by peritumoral brain edema before operative. a and c, patients only take a resection of the tumor. b and d, patients remove the tumor and give an excision with PTBE.

Figure 4

GBM recurrence in patients undergoing PTBE resection is slower than that of PTBE without resection. All the patients are accompanied by peritumoral brain edema before operative. a, patients remove the tumor and give an excision with PTBE, the tumor recurred during the 6^rd month after operative. b, patients only take a resection of the tumor, the tumor recurred during the 3^rd month after operative.

Figure 5

Abnormal expression of tumor-associated proteins in PTBE region. a-d, Western blotting analysis of p-AKT and p-ERK 1/2 (a); P53 and PTEN (b); GLUT1, c-Myc, LDHA, PGK1and PKM2 (c); NLGN3 (d) in human brain tissues (*P < 0.05 versus the Normal). Data are expressed as mean ± SE. Statistical analysis was implemented by student's t-test and variance analysis.