Role of Radiation Therapy in the Management of Diffuse Intrinsic Pontine Glioma: A Systematic Review

Abstract

Purpose Diffuse intrinsic pontine glioma (DIPG) is the most aggressive primary pediatric brain tumor, with <10% of children surviving 2 years. Radiation therapy (RT) remains the mainstay of treatment, but there is a great clinical need for improvements and advancements in treatment strategies. The aim of this systematic review was to identify all available studies in which RT was used to treat patients with DIPG. Methods and Materials A literature search for studies published up to March 10, 2018 was conducted using the PubMed database. We identified 384 articles using search items “diffuse intrinsic pontine glioma” and 221 articles using search items “diffuse brainstem glioma radiotherapy.” Included studies were prospective and retrospective series that reported outcomes of DIPG treatment with RT. Results We identified 49 studies (1286 patients) using upfront conventionally fractionated RT, 5 studies (92 patients) using hypofractionated RT, and 8 studies (348 patients) using hyperfractionated RT. The mean median overall survival (OS) was 12.0 months, 10.2 months, and 7.9 months in patients who received conventional, hyperfractionated, and hypofractionated RT regimens, respectively. Patients undergoing radiosensitizing therapy had a mean median OS of 11.5 months, and patients who did not receive concomitant systemic therapy had an OS of 9.4 months. In patients who received salvage RT, the mean median OS from initial diagnosis was 16.3 months. Conclusions As one of the largest systematic reviews examining RT for DIPG, this report may serve as a useful tool to help clinicians choose the most appropriate treatment approach, while also providing a platform for future investigations into the utility of RT and systemic therapy.

Advanced ADC Histogram, Perfusion, and Permeability Metrics Show an Association with Survival and Pseudoprogression in Newly Diagnosed Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium

“…2 Radiation therapy (RT) has shown transient improvement of neurologic symptoms and marginal survival benefit. 3 In this study, we assessed associations between survival and imaging metrics derived from advanced diffusion, perfusion, and permeability MR imaging data in a cohort of patients with newly diagnosed DIPG treated with veliparib concurrent with RT, followed by maintenance therapy of veliparib plus temozolomide (TMZ) treated in a Pediatric Brain Tumor Consortium (PBTC) Phase I/II trial. Poly (adenosine diphospate ribose) polymerase (PARP) inhibitors such as veliparib have been shown to overcome TMZ resistance while also increasing radiosensitivity.…”

Hypofractionated radiotherapy versus conventional radiotherapy for diffuse intrinsic pontine glioma

“…Hu et al [ 30 ] performed a systematic review of the Cochrane database to identify phase III randomized controlled trials, although their review only identified the Zaghloul et al [ 8 ] study. Gallitto et al [ 31 ] also performed a systematic review that compared CFRT, HFRT, and hyperfractionated radiotherapy for DIPG. Their search identified 49 CFRT, 7 hyperfractionated radiotherapy, and 3 HFRT studies, although they failed to detect significant differences between HFRT and CFRT in terms of the median OS (9.0 months vs 9.4 months) and time to progression (5.0 months vs 7.6 months).…”

Radio-Resistance and DNA Repair in Pediatric Diffuse Midline Gliomas

“…Similarly, radio-sensitizers (e.g., carbogen, motefaxin gadolinium) did not improve the survival of DMG patients [ 21 , 22 ]. Currently in clinical trials for DMGs are inhibitors of histone deacetylases (HDAC), which emerged from functional screen data as well as the observation of consistently elevated histone acetylation in a number of studies [ 23 ].…”