High-grade glioma in infants and young children is histologically, molecularly, and clinically diverse: Results from the SJYC07 trial and institutional experience.
Neuro Oncol
; 26(1): 178-190, 2024 01 05.
Article
in En
| MEDLINE
| ID: mdl-37503880
ABSTRACT
BACKGROUND:
High-grade gliomas (HGG) in young children pose a challenge due to favorable but unpredictable outcomes. While retrospective studies broadened our understanding of tumor biology, prospective data is lacking.METHODS:
A cohort of children with histologically diagnosed HGG from the SJYC07 trial was augmented with nonprotocol patients with HGG treated at St. Jude Children's Research Hospital from November 2007 to December 2020. DNA methylome profiling and whole genome, whole exome, and RNA sequencing were performed. These data were integrated with histopathology to yield an integrated diagnosis. Clinical characteristics and preoperative imaging were analyzed.RESULTS:
Fifty-six children (0.0-4.4 years) were identified. Integrated analysis split the cohort into four categories infant-type hemispheric glioma (IHG), HGG, low-grade glioma (LGG), and other-central nervous system (CNS) tumors. IHG was the most prevalent (nâ =â 22), occurred in the youngest patients (median ageâ =â 0.4 years), and commonly harbored receptor tyrosine kinase gene fusions (7 ALK, 2 ROS1, 3 NTRK1/2/3, 4 MET). The 5-year event-free (EFS) and overall survival (OS) for IHG was 53.13% (95%CI 35.52-79.47) and 90.91% (95%CI 79.66-100.00) vs. 0.0% and 16.67% (95%CI 2.78-99.74%) for HGG (pâ =â 0.0043, pâ =â 0.00013). EFS and OS were not different between IHG and LGG (pâ =â 0.95, pâ =â 0.43). Imaging review showed IHGs are associated with circumscribed margins (pâ =â 0.0047), hemispheric location (pâ =â 0.0010), and intratumoral hemorrhage (pâ =â 0.0149).CONCLUSIONS:
HGG in young children is heterogeneous and best defined by integrating histopathological and molecular features. Patients with IHG have relatively good outcomes, yet they endure significant deficits, making them good candidates for therapy de-escalation and trials of molecular targeted therapy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Neoplasms
/
Glioma
Type of study:
Guideline
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Child
/
Child, preschool
/
Humans
/
Infant
Language:
En
Journal:
Neuro Oncol
Journal subject:
NEOPLASIAS
/
NEUROLOGIA
Year:
2024
Document type:
Article
Affiliation country: