Nimotuzumab as Additional Therapy for GLIOMA in Pediatric and Adolescent: A Systematic Review

Abstract

Introduction: Pediatric gliomas represent the most common brain tumor in children and its higher grades are associated with higher recurrence and low survival rate. All therapeutic modalities are reported to be insufficient to achieve satisfactory result, with follow-up treatment such as adjuvant radiotherapy and chemotherapy recommended to increase survival and hinder tumor progression. Nimotuzumab is a monoclonal antibody that acts as an inhibitor of epidermal growth factor receptor found on the surface of glioma cells and had been studied for its usage in pediatric gliomas in recent years.

Methods: A systematic review is performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A through literature search was conducted on PubMed, Scopus, Cochrane, and clinicaltrials.gov database. Articles were selected systematically based on the PRISMA protocol and reviewed completely. The relevant data were summarized and discussed. We measured overall survival, progression-free survival, and adverse Events (AE) for nimotuzumab usage as an adjunct therapy in pediatric glioma population.

Result: From 5 studies included for qualitative analysis, 151 patients are included with overall survival (OS) that vary from 3.2-22.8 mo, progression-free survival (PFS) from 1.7-21.6 mo, and relatively low serious adverse events (0-21) are recorded. Follow-up ranged from 2.4-66 mo with four studies reporting diffuse intrinsic pontine glioma (DIPG) patients and only one study reporting nimotuzumab usage in pediatric high-grade glioma (HGG) patients with better outcome in HGG patients than DIPG.

Conclusion: There are no significant differences in the PFS and OS of nimotuzumab as adjunct therapy for pediatric compared to result of standard therapy in majority of previous studies. There were also no differences in the AE of nimotuzumab for pediatric glioma between studies, and low event of serious adverse events indicating its safety. But still there is an evidence of possible benefit of nimotuzumab as adjuvant therapy in pediatric glioma. We recommend further studies with larger number of patients that may lead to possibly different results. There should also be more studies with better level of evidence to further validate the effect of nimozutumab on pediatric glioma.

Keywords: Brain Tumor; Cancer; Child Mortality; Glioma; Immunology.

Figure 1.

PRISMA flow diagram.

Figure 2.

Result of ROBINS-I assesment. A, Risk assessment of bias using ROBINS-I for non-randomized studies in each study. B, the proportion of bias risk assessment results using ROBINS-I for the non-randomized study.