MR imaging features of diffuse intrinsic pontine glioma and relationship to overall survival: report from the International DIPG Registry (original) (raw)
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American Journal of Neuroradiology, 2020
BACKGROUND AND PURPOSE: Recent advances in molecular techniques have characterized distinct subtypes of diffuse intrinsic pontine gliomas. Our aim was the identification of MR imaging correlates of these subtypes. MATERIALS AND METHODS: Initial MRIs from subjects with diffuse intrinsic pontine gliomas recruited for a prospective clinical trial before treatment were analyzed. Retrospective imaging analyses included FLAIR/T2 tumor volume, tumor volume enhancing, the presence of cyst and/or necrosis, median, mean, mode, skewness, kurtosis of ADC tumor volume based on FLAIR, and enhancement at baseline. Molecular subgroups based on EGFR and MGMT mutations were established. Histone mutations were also determined (H3F3A, HIST1H3B, HIST1H3C). Univariate Cox proportional hazards regression was used to test the association of imaging predictors with overall and progression-free survival. Wilcoxon rank sum, Kruskal-Wallis, and Fisher exact tests were used to compare imaging measures among groups. RESULTS: Fifty patients had biopsy and MR imaging. The median age at trial registration was 6 years (range, 3.3-17.5 years); 52% were female. On the basis of immunohistochemical results, 48 patients were assigned to 1 of 4 subgroups: 28 in MGMT-/epidermal growth factor receptor (EGFR)-, 14 in MGMT-/EGFR+, 3 in MGMT+/EGFR-, and 3 in MGMT+/EGFR+. Twenty-three patients had histone mutations in H3F3A, 8 in HIST1H3B, and 3 in HIST1H3C. Enhancing tumor volume was near-significantly different across molecular subgroups (P = .04), after accounting for the false discovery rate. Tumor volume enhancing, median, mode, skewness, and kurtosis ADC T2-FLAIR/T2 were significantly different (P # .048) between patients with H3F3A and HIST1H3B/C mutations. CONCLUSIONS: MR imaging features including enhancement and ADC histogram parameters are correlated with molecular subgroups and mutations in children with diffuse intrinsic pontine gliomas. ABBREVIATIONS: DIPG = diffuse intrinsic pontine glioma; EGFR = epidermal growth factor receptor; FDR = false discovery rate; PFS = progression-free survival; PG = postgadolinium; OS = overall survival D iffuse intrinsic pontine glioma (DIPG) is a malignant brain tumor that accounts for 75%-80% of brain stem tumors in children. 1 Despite medical therapy, these tumors have a poor prognosis, with a median survival at 1, 2, and 3 years of 41%, 15.3%, and 7.2%, respectively. 2 The 2016 World Health Organization classification of brain tumors introduced the term "diffuse midline glioma, H3 K27M mutant" to describe these neoplasms due to the high prevalence of unique histone protein mutations that differ from those of supratentorial (hemispheric) pediatric high-grade gliomas and adult high-grade gliomas. While H3 K27M is the most common variant detected, more recently, other distinct histone mutations have been
Diagnostics and treatment of diffuse intrinsic pontine glioma: where do we stand?
Journal of Neuro-Oncology, 2019
Introduction Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. Methods Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. Results Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatmen...
The Egyptian Journal of Radiology and Nuclear Medicine, 2013
Background: Pediatric diffuse intrinsic pontine glioma (DIPG) remains dismal regardless the new therapeutic and technical advances. Objective: To investigate the value of magnetic resonance imaging (MRI) in predicting DIPG prognosis. Patients and methods: Twenty-five DIPG patients with 95 (initial and post radiotherapy) MR examinations were studied. Hydrocephalus was detected in 6 cases (24%), basilar artery encasement in 20 (80%), ill defined border in 16 (64%), perilesional edema in 2 cases (8%) and none showed leptomeningeal spread. Conformal 3-dimensional radiotherapy (39 Gy/13 fractions or 54 Gy/30 fractions) was applied. Results: The median overall survival (MOS) was 9.3 months (95% CI: 7.9-10.8) and the one year overall survival was 18 ± 8.9%. Post radiation MRI performed 3-6 months after treatment showed regression in 8 cases (32%), stationary course in 5 (20%) and progression in 12 cases (48%). The MOS was higher in children whose MRI showed regression (10.0, CI: 6.3-13.7) than those with
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2018
Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, ...
Neuro-oncology, 2017
Diffuse intrinsic pontine glioma (DIPG) has proven to be one of the most challenging of all pediatric cancers. Owing to a historical reticence to obtain tumor tissue for study, and based on an erroneous assumption that the biology of DIPG would mirror that of supratentorial high-grade astrocytomas, innumerable studies have been undertaken-all of which have had a negligible impact on the natural history of this disease. More recently, improvements in neurosurgical techniques have allowed for the safe upfront biopsy of DIPG, which, together with a wider use of autopsy tissue, has led to an evolving understanding of the biology of this tumor. The discovery of a recurrent somatic gain-of-function mutation leading to lysine 27 to methionine (p.Lys27Met, K27M) substitution in histone 3 variants characterizes more than 85% of DIPG, suggesting for the first time the role of the epigenome and histones in the pathogenesis of this disease, and more unified diagnostic criteria. Along with furth...
Diffuse intrinsic pontine glioma: current insights and future directions
Chinese Neurosurgical Journal, 2021
Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain tumor and the leading cause of brain tumor–related death in children. As several clinical trials over the past few decades have led to no significant improvements in outcome, the current standard of care remains fractionated focal radiation. Due to the recent increase in stereotactic biopsies, tumor tissue availabilities have enabled our advancement of the genomic and molecular characterization of this lethal cancer. Several groups have identified key histone gene mutations, genetic drivers, and methylation changes in DIPG, providing us with new insights into DIPG tumorigenesis. Subsequently, there has been increased development of in vitro and in vivo models of DIPG which have the capacity to unveil novel therapies and strategies for drug delivery. This review outlines the clinical characteristics, genetic landscape, models, and current treatments and hopes to shed light on novel therapeutic avenues and challenges ...
The Molecular, Neurological, and Clinical Features of Diffuse Intrinsic Pontine Glioma
Diffuse intrinsic pontine glioma (DIPG) is recognized as a pediatric brainstem cancer with a 0% survival rate. On a molecular basis, DIPG commonly results from mutations in histone H3, specifically a mutation in the H3K27M gene, that promotes tumorigenesis and results in presentation of this fatal brainstem tumor. DIPG is challenging to treat, as surgical intervention is inefficacious due to the location where the glioma resides. To date, traditional treatments such as radiation, chemotherapy, and immunotherapy have not increased survival rates and have only been successful at relieving symptoms. Future therapeutic approaches such as proton beam radiation, Chimeric Antigen Receptor T Cell (CAR-T) immunotherapy, and alternative epigenetic pharmaceuticals are under investigation for potential benefits. Various clinical trials have also explored these treatment procedures to discover potential increases in survival rates in both animal and human studies. In this review, we will evaluat...