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.

Fig 1.

Flowchart of patients excluded from this study. DIPG, diffuse intrinsic pontine glioma.

Fig 2.

Clinical, histologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma. Bev, bevacizumab; CN, cranial nerve; CRO, Croatia; DIPG, International DIPG Registry; EGFR, epidermal growth factor receptor; FR, France; GER, Germany, Switzerland, Austria; GOSH, Great Ormond Street Hospital; HDAC, histone deacetylase inhibitor; IT, Italy; LFU, last follow-up; mTOR, mammalian target of rapamycin inhibitor; NETH, the Netherlands; OS, overall survival; Re-RT, reirradiation; RT, radiation therapy; UK, United Kingdom; Unkn, unknown.

Fig 3.

Kaplan-Meier curves representing overall survival (OS) based on (A) patient age (years), (B) symptom duration (weeks), (C) systemic therapy at diagnosis, (D) WHO grade, or (E) histone status. WT, wild type.

Fig 4.

Genomic aberrations in long-term survivors of diffuse intrinsic pontine glioma (DIPG). DIPG, International DIPG Registry; FR, France; GER, Germany, Switzerland, Austria; NETH, the Netherlands; OS, overall survival.

Fig A1.

Very long–term survivors of diffuse intrinsic pontine glioma in the current study compared with those described in the literature. Yellow highlight indicates atypical radiologic features that would have been excluded in the current study. Bev, bevacizumab; CN, cranial nerve; DIPG, diffuse intrinsic pontine glioma; EGFR, epidermal growth factor; GER, Germany, Switzerland, Austria; GOSH, Great Ormond Street Hospital; HDAC, histone deacetylase inhibitor; HGG, high-grade glioma; IDIPGR, International Diffuse Intrinsic Pontine Glioma Registry; IT, Italy; LFU, last follow-up; NCI, National Cancer Institute; NETH, the Netherlands; OS, overall survival; POG, Pediatric Oncology Group; Re-RT, reirradiation; RT, radiation therapy; SIOPE, European Society for Pediatric Oncology; SJCRH, St Jude Children's Research Hospital; UK, United Kingdom; WT, wild type.

Fig A2.

(A) Comparison of characteristics of patients who received therapy or did not receive therapy at diagnosis. (B) Magnetic resonance images and clinical characteristics of two long-term survivors (LTSs) of diffuse intrinsic pontine glioma who did not receive therapy. CN, cranial nerve; GER, Germany, Switzerland, Austria; LFU, last follow-up; NETH, the Netherlands; OS, overall survival; Re-RT, reirradiation; RT, radiation therapy.

Fig A3.

Clinical, radiologic, and molecular characteristics of patients with diffuse intrinsic pontine glioma age > 18 years. Bev, bevacizumab; CN, cranial nerve; DIPG, International DIPG Registry; EGFR, epidermal growth factor; FR, France; GER, Germany, Switzerland, Austria; HDAC, histone deacetylase inhibitor; IT, Italy; LFU, last follow-up; OS, overall survival; Re-RT, reirradiation; RT, radiation therapy; WT, wild type.