Emerging Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma: A Systematic Review

Abstract

Background: Of all central nervous systems tumors, 10–20% are located in the brainstem; diffuse intrinsic pontine glioma (DIPG) is diagnosed in 80% of them. With over five decades of clinical trial testing, there are no established therapeutic options for DIPG. This research article aims to collate recent clinical trial data and provide a landscape for the most promising therapies that have emerged in the past five years. Methods: PubMed/MEDLINE, Web of Science, Scopus, and Cochrane were systematically searched using the following keywords: Diffuse intrinsic pontine glioma, Pontine, Glioma, Treatment, Therapy, Therapeutics, curative, and/or Management. Both adult and pediatric patients with newly diagnosed or progressive DIPG were considered in the clinical trial setting. The risk of bias was assessed using the ROBINS-I tool. Results: A total of 22 trials were included reporting the efficacy and safety outcomes among patients. First, five trials reported outcomes of blood–brain barrier bypass via single or repeated-dose intra-arterial therapy or convection-enhanced delivery. Second, external beam radiation regimens were assessed for safety and efficacy in three trials. Third, four trials administered intravenous treatment without using chemotherapeutic regimens. Fourth, eight trials reported the combinations of one or more chemotherapeutic agents. Fifth, immunotherapy was reported in two trials in an adjuvant monotherapy in the post-radiotherapy setting. Conclusion: This research article captures a clinical picture of the last five years of the direction toward which DIPG research is heading. The article finds that re-irradiation may prolong survival in patients with progressive DIPG; it also instills that insofar palliative radiotherapy has been a key prognostic choice.

Epidemiology, Diagnostic Strategies, and Therapeutic Advances in Diffuse Midline Glioma

“…Diffuse midline glioma (DMG) is a type of malignant tumor derived from glial cells, primarily occurring in children. It is characterized by a diffuse infiltrative growth of tissue affecting the brain stem, which often renders surgical resection unfeasible [ 1 ]. Brain stem tumors are relatively prevalent among children, accounting for approximately one in five cases of nervous system tumors in this age group.…”

“…In the past decade, the primary method for diagnosing DMG has been magnetic resonance imaging (MRI) [ 1 , 2 , 3 , 4 , 10 ]. The tumor grows within the brain stem, responsible for vital functions like breathing, heart rate, and blood pressure.…”

“…Despite being classified as a rare tumor, DMG accounts for approximately 10–15% of all brain tumor deaths in children, representing one of the most important causes of tumor-related deaths in this age group [ 1 , 11 , 12 ], so is particularly relevant today due to the high mortality rate and the lack of effective therapeutic options. DMG has emerged as a compelling subject of scientific investigation, particularly in the realm of clinical studies and trials aimed at assessing novel therapeutic approaches such as immunotherapy, T-cell therapy, and targeted therapies.…”