Characteristics of children ≤36 months of age with DIPG: A report from the international DIPG registry

Abstract

Background Children ≤36 months with Diffuse Intrinsic Pontine Glioma (DIPG) have increased long-term survival (LTS, overall survival (OS) ≥24 months). Understanding distinguishing characteristics in this population is critical to improving outcomes. Methods Patients ≤36 months at diagnosis enrolled on the International DIPG Registry (IDIPGR) with central imaging confirmation were included. Presentation, clinical course, imaging, pathology and molecular findings were analyzed. Results Among 1183 patients in IDIPGR, 40 were eligible (median age: 29 months). Median OS was 15 months. Twelve patients (30%) were LTS, 3 (7.5%) very long-term survivors ≥ 5 years. Among 8 untreated patients, median OS was 2 months. Patients enrolled in the registry but excluded from our study by central radiology review or tissue diagnosis had median OS of 7 months. All but 1 LTS received radiation. Among 32 treated patients, 1-, 2-, 3-, and 5-year OS rates were 68.8%, 31.2%, 15.6% and 12.5%, respectively. LTS had longer duration of presenting symptoms (p=0.018). No imaging features were predictive of outcome. Tissue and genomic data were available in 18 (45%) and 10 patients, respectively. Among 9 with known H3K27M status, 6 had a mutation. Conclusions Children ≤36 months demonstrated significantly more LTS, with an improved median OS of 15 months; 92% of LTS received radiation. Median OS in untreated children was 2 months, compared to 17 months for treated children. LTS had longer duration of symptoms. Excluded patients demonstrated a lower OS, contradicting the hypothesis that children ≤36 months with DIPG show improved outcomes due to misdiagnosis.

Very Long-Term Survivorship in Pediatric DIPG: Case Report and Review of the Literature

“…DIPGs classically present with a rapid onset of neurological symptoms, with a median age at diagnosis of 6-7 years. 2,5,8-10,13 Our patient's progressive symptomatology over one year 4,8,12 and her relatively old age at the time of diagnosis were indicative of her potential for long-term survival. 2,4,6 Other known clinical factors that favor LTS include the lack of cranial nerve palsies at the time of diagnosis 4,9,12,13 ; however, this was not the case for our patient.…”

“…Bartlett et al did not find any MRI findings (tumor dimensions and extension, margins, presence of hemorrhage, diffusion restriction, enhancement morphology, degree of necrosis and hydrocephalus) predictive of survivorship, except for an absence of spinal metastases. 12 However, other authors determined that ring enhancements, 8,9,12,13 significant necrosis, 4,6,9 extrapontine extension 4 , and greater craniocaudal dimensions (other planes were insignificant 6 ) are unfavorable prognostic factors. 9 Research on MRI variables as dynamic biomarkers for progression-free survival is ongoing in DIPG, [14][15][16] although the direct role of routine follow-up imagery on survival remains unclear.…”

“…IDH1 mutant tumors tend to occur in children older than 14 years and can predict a better prognosis. 6,9,12 Porkholm et al reported another IDH1 mutant DIPG patient with OS of 7.5 years. 1 The authors hypothesize that the IDH1 mutation may provoke a slower evolution in histological grade, concordant with our patients' exceptional survivorship and long progression-free periods.…”

Differences in survival prognosticators between children and adults with H3K27M‐mutant diffuse midline glioma

“…An earlier study with 316 pediatric patients showed that age ≤3 years positively predicted the prognosis of DIPG. 43 Moreover, an international cohort demonstrated that DIPG patients aged ≤36 months had increased long-term survival, 44 and suggested that patients of different ages could have different prognoses, especially within the pediatric group. A recent study profiled the landscape of cell states and tumor microenvironment, which were found to be different in H3K27M-mutant DMG between the pediatric and adult patients, 45 probably accounting for the different prognoses.…”

Pediatric diffuse midline glioma H3K27- altered: A complex clinical and biological landscape behind a neatly defined tumor type

“…On the opposite side of the epidemiological spectrum of age, it has been reported that very young children with DMG (less than three years old) might have a significantly longer OS than older patients ( 42 , 67 ).…”