Clinical, Radiologic, Pathologic, and Molecular Characteristics of Long-Term Survivors of Diffuse Intrinsic Pontine Glioma (DIPG): A Collaborative Report From the International and European Society for Pediatric Oncology DIPG Registries

Abstract

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, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.

Identification of prognostic markers in diffuse midline gliomas H3K27M‐mutant

“…A total of 35 patients (79.5%) were identified with H3F3A or HIST1H3B mutation (Figure 2). In this subgroup, the median age at diagnosis was 9 years (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), and the median overall survival was 7.9 months ( IQR 3,8;13,9). Twenty-three patients (65.7%) had a tumor exclusively located in the brainstem, whereas 8 patients (22.9%) had a tumor in another midline location, as described previously.…”

“…Due to their location, complete surgical removal is impossible. Treatment is essentially based on radiation therapy given that successive clinical trials have not identified a benefit from adjuvant or neoadjuvant chemotherapy (1,14,20). Unfortunately, radiation therapy remains palliative and only increases survival by 3-4 months (20).…”

Hypoxia Inducible Factors’ Signaling in Pediatric High-Grade Gliomas: Role, Modelization and Innovative Targeted Approaches

“…Typical DIPG images have depicted it as arising from the brainstem and being diffusively involved in more than half of the pons. Surprisingly Hoffmann et al found that the MRIs of short-term survivors were associated with a low necrosis percentage but a less frequent ring enhancement [50]. All those studies might explain a balance between level of hypoxic zones, neoangiogenesis and the high diffusive phenotype of the pHGG cells side to side with normal neurons and fibers, especially in pons.…”

Challenging the indiscriminate use of temozolomide in pediatric high‐grade gliomas: A review of past, current, and emerging therapies

“…Additionally, this challenge highlights the need for international collaboration at a global scale. For instance, the joint report of the International and European Society for Pediatric Oncology DIPG Registries, which gathered comprehensively annotated information on more than 1000 cases of DIPG and the integrated molecular meta‐analysis of 1000 pHGG and DIPG constitute successful examples of large‐scale transatlantic collaborations. Translation of these joint initiatives into collaborative randomized clinical trials will be essential to conduct biomarker‐driven studies for specific subsets of pHGG.…”